Application of bifidobacterium lactis TY-S01 or product thereof in preparation of preparation for preventing or improving or treating diabetes

Abstract

The invention belongs to the technical field of bacterial strain application, and particularly relates to application of bifidobacterium lactis TY-S01 or a product thereof in preparation of a preparation for preventing or improving or treating diabetes. Animal experiments prove that the bifidobacterium lactis TY-S01 can obviously relieve diabetes characteristics (weight loss and water intake increase) of type II diabetic mice, obviously reduce fasting blood-glucose level, obviously improve insulin resistance and serum insulin level, obviously reduce serum glycosylated hemoglobin A1c level, serum Glu level and serum TG level, and can obviously inhibit the diabetes mellitus of the type II diabetic mice, so that the bifidobacterium lactis TY-S01 can be used for treating diabetes mellitus of the type II diabetic mice. The pathological injury of pancreatic tissues is obviously improved; the serum ALT level and the serum AST level can be obviously reduced, the pathological injury of liver tissues is obviously improved, and a certain protection effect is achieved on the liver.

Description

Technical Field

[0001] The invention belongs to the technical field of strain application, and specifically relates to an application of Bifidobacterium lactis TY-S01 or a product thereof in preparing a preparation for preventing, improving or treating diabetes. Background Art

[0002] Diabetes is a chronic metabolic disease caused by genetic and environmental factors. Long-term high blood sugar in diabetes can cause chronic damage and dysfunction of the eyes, kidneys, liver, heart, blood vessels, and nerves, which may eventually lead to blindness, complications such as uremia, stroke, and myocardial infarction, and even endanger life. Diabetes is mainly divided into two types according to different pathogenic mechanisms: insufficient insulin secretion (type I) and insulin resistance (type II). Type II diabetes accounts for about 90% of diabetic patients. It is a chronic disease caused by the combined effects of genetic inheritance and environmental factors, and is mainly manifested as insulin resistance, progressive increase in blood sugar, and decreased glucose tolerance. However, there are two main treatment strategies at present. One is insulin injection, but this therapy may lead to insulin resistance; the other is oral hypoglycemic drugs. The main oral hypoglycemic drugs include insulin secretion promoters (mainly including sulfonylurea drugs, phenylalanine derivatives and glucagon-like peptide-1 (GLP-1)), insulin sensitizers (including thiazolidinediones and biguanides), α-glucosidase inhibitors (voglibose, miglitol and acarbose), etc. Although these drugs can be used for symptomatic treatment, they have many adverse reactions (diarrhea, dry mouth, headache, etc.). Therefore, it is of great significance to develop efficient and safe functional products to prevent, alleviate or treat diabetes.

[0003] Probiotics are a type of active microorganisms that colonize the human intestine and are beneficial to the host. They have excellent safety, and some animal experiments and clinical experimental studies have confirmed that some probiotics can prevent and treat type 2 diabetes without causing other side effects, such as the Ganoderma lucidum strain SS30 with a preservation number of CGMCC No. 23283 recorded in patent CN114259508A, the Lactobacillus plantarum AR113 strain with a preservation number of CGMCC No. 13909 recorded in patent CN111304134A, and the Lactobacillus murinus with a preservation number of CICC23140 recorded in patent CN114561318A.

[0004] Therefore, discovering a strain that can prevent, alleviate or treat diabetes is of great significance for the prevention and treatment of type 2 diabetes. Summary of the invention

[0005] The present invention finds that Bifidobacterium lactis TY-S01 with a preservation number of CGMCC No. 21255 can significantly alleviate the diabetic characteristics of diabetic mice (weight loss and increased water intake), significantly reduce fasting blood sugar levels, significantly improve insulin resistance and serum insulin levels, significantly reduce serum glycosylated hemoglobin A1c levels, serum Glu levels and serum TG levels, and significantly improve pathological damage to pancreatic tissue; it can also significantly reduce serum ALT levels and serum AST levels, and significantly improve pathological damage to liver tissue; therefore, Bifidobacterium lactis TY-S01 can be used in the regulation of blood sugar levels, insulin levels, etc.

[0006] In order to achieve the above object, the present invention can adopt the following technical solutions:

[0007] On one hand, the present invention provides a use of Bifidobacterium lactis TY-S01 or a product thereof in preparing a medicament for preventing or improving diabetes. The preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01.

[0008] Preferably, in the above application, diabetes is type 2 diabetes.

[0009] Preferably, in the above applications, the applications include one or more of the following applications: (a) application of Bifidobacterium lactis or its preparation in the preparation of a medicament for alleviating weight loss and / or increased water intake caused by diabetes; (b) application of Bifidobacterium lactis TY-S01 or its preparation in the preparation of a medicament for lowering blood sugar levels; (c) application of Bifidobacterium lactis TY-S01 or its preparation in the preparation of a medicament for lowering insulin levels; (d) application of Bifidobacterium lactis TY-S01 or its preparation in the preparation of a medicament for lowering insulin resistance; (e) application of Bifidobacterium lactis TY-S01 or its preparation in the preparation of a medicament for lowering glycated hemoglobin levels; (f) application of Bifidobacterium lactis TY-S01 or its preparation in the preparation of a medicament for improving pancreatic and / or liver damage caused by diabetes.

[0010] Preferably, in the above application, the dosage form of the drug is tablet, powder, granule, capsule, emulsion, gel or liquid dosage form.

[0011] On the other hand, the present invention also provides an application of Bifidobacterium lactis TY-S01 or its product in preparing a health food, wherein the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the health food has one or more of the following functions: (a) helping to maintain a healthy blood sugar level; (b) helping to maintain a healthy blood lipid level; (c) helping to assist in protecting the pancreas and / or liver damage caused by diabetes; and (d) helping to maintain a healthy insulin level.

[0012] Preferably, in the above application, the dosage form of the health food is tablet, powder, granule, capsule, emulsion, gel or liquid dosage form.

[0013] In another aspect, the present invention provides a use of Bifidobacterium lactis TY-S01 or a product thereof in preparing a functional food. The preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the functional food has one or more of the following functions: (a) helps maintain a healthy blood sugar level; (b) helps maintain a healthy blood lipid level; (c) helps to assist in protecting the pancreas and / or liver damage caused by diabetes; (d) helps to maintain a healthy insulin level.

[0014] Preferably, in the above application, the functional food is a liquid food, a semi-solid food or a solid food.

[0015] The beneficial effects of the present invention include: animal experiments have confirmed that Bifidobacterium lactis TY-S01 can significantly alleviate the diabetic characteristics of type 2 diabetic mice (weight loss and increased water intake), significantly reduce fasting blood sugar levels, significantly improve insulin resistance and serum insulin levels, significantly reduce serum glycosylated hemoglobin A1c levels, serum Glu levels and serum TG levels, and significantly improve pathological damage to pancreatic tissue; it can also significantly reduce serum ALT levels and serum AST levels, significantly improve pathological damage to liver tissue, and has a certain protective effect on the liver. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The figures are the weight change trend (A), final weight (B), and average daily food intake (C) and water intake (D) of each mouse during the treatment period.

[0017] Figure 2 The effect of Bifidobacterium lactis TY-S01 on fasting blood glucose level in type Ⅱ diabetic mice;

[0018] Figure 3 Effects of Bifidobacterium lactis TY-S01 on glucose tolerance (A) and the area under the curve (B) in type Ⅱ diabetic mice;

[0019] Figure 4 Effects of Bifidobacterium lactis TY-S01 on serum insulin (A) and HOMA-IR (insulin resistance index) (B) in type Ⅱ diabetic mice;

[0020] Figure 5 The effect of Bifidobacterium lactis TY-S01 on serum HbA1c (glycosylated hemoglobin) level in type Ⅱ diabetic mice;

[0021] Figure 6 The effect of Bifidobacterium lactis TY-S01 on serum Glu (glucose) level in type Ⅱ diabetic mice;

[0022] Figure 7 The effect of Bifidobacterium lactis TY-S01 on serum TG (triglyceride) level in type Ⅱ diabetic mice;

[0023] Figure 8 Effects of Bifidobacterium lactis TY-S01 on serum ALT (alanine aminotransferase) (A) and AST (aspartate aminotransferase) (B) levels in type Ⅱ diabetic mice;

[0024] Fig. 9 The effect of Bifidobacterium lactis TY-S01 on pancreatic histopathology in type Ⅱ diabetic mice;

[0025] Fig.10 The effect of Bifidobacterium lactis TY-S01 on liver histopathology in type Ⅱ diabetic mice;

[0026] In the above figures, different lowercase letters indicate significant differences between the two groups (p<0.05). DETAILED DESCRIPTION

[0027] The examples are provided to better illustrate the present invention, but the present invention is not limited to the examples. Therefore, those skilled in the art may make non-essential improvements and adjustments to the implementation scheme according to the above invention content, which still fall within the protection scope of the present invention.

[0028] The terms used herein are only used to describe specific embodiments and are not intended to limit the present disclosure. Unless the context has a significantly different meaning, expressions in the singular include expressions in the plural. As used herein, it should be understood that terms such as "include", "have", "include" are intended to indicate the presence of features, numbers, operations, materials, or combinations. The terms of the present invention are disclosed in the specification, and are not intended to exclude the possibility that one or more other features, numbers, operations, materials, or combinations thereof may exist or may be added. As used herein, " / " may be interpreted as "and" or "or", depending on the circumstances.

[0029] In the present invention, Bifidobacterium lactis TY-S01 originates from Chongqing Tianyou Dairy Co., Ltd. The strain is recorded in patent 202111569073.9. The strain is deposited in the General Microbiology Center of China National Microbiological Culture Collection Administration (CGMCC) with a deposit number of CGMCC No. 21255 and a deposit date of November 27, 2020.

[0030] In the present invention, it should be noted that on August 18, 2022, the National Health Commission issued the "In accordance with the relevant provisions of the "Food Safety Law of the People's Republic of China" and its implementing regulations, in order to further standardize the management of the "List of Bacteria that Can Be Used in Food" and the "List of Bacteria that Can Be Used in Infant Food", the review agency organized experts to update the two lists of bacteria. For the classification and naming adjustments of bacteria in the list, a 2-year transition period is set. "For the updated announcement, please refer to the website: http: / / www.nhc.gov.cn / sps / s7892 / 202208 / 1d6c229d6f744b35827e98161c146afb.shtml, among which, the "Bifidobacterium lactis (Latin: Bifidobacterium lactis)" in the "List of Bacteria that Can Be Used in Food" was changed to "Bifidobacterium animalis subspecies subsp. lactis)", and it can be known from the above that the Bifidobacterium lactis TY-S01 in the present invention can also be called animal Bifidobacterium lactis subsp. TY-S01, which is a strain that can be used in food, indicating that it has no toxic side effects and is safe.

[0031] In the present invention, "culture" refers to a collection of microbial cell groups or growths of a certain strain within a certain time and space; "metabolites" refer to a variety of chemical substances produced by the strain in the metabolic process, which can be primary metabolites (such as sugars, amino acids, nucleotides, etc., which are necessary for the growth and reproduction of microorganisms) or secondary metabolites (such as antibiotics, vitamins, enzymes, etc.); "bacterial suspension" refers to a suspension containing microbial cells of a strain; "bacterial powder" refers to a powdery substance obtained by drying the culture of a strain (such as spray drying, freeze drying, etc.); "fermentation broth" refers to a liquid obtained by inoculating a strain into a liquid culture medium and fermenting it for a period of time.

[0032] The embodiment of the present invention provides a use of Bifidobacterium lactis TY-S01 or a product thereof in preparing a medicament for preventing or improving diabetes. The preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01.

[0033] In some specific examples, in the above applications, diabetes is type 2 diabetes.

[0034] In some specific examples, the above-mentioned applications include one or more of the following applications: (a) use of Bifidobacterium lactis or its products in the preparation of drugs for alleviating weight loss and / or increased water intake caused by diabetes; (b) use of Bifidobacterium lactis TY-S01 or its products in the preparation of drugs for lowering blood sugar levels; (c) use of Bifidobacterium lactis TY-S01 or its products in the preparation of drugs for lowering insulin levels; (d) use of Bifidobacterium lactis TY-S01 or its products in the preparation of drugs for lowering insulin levels; (e) use of Bifidobacterium lactis TY-S01 or its products in the preparation of drugs for lowering glycated hemoglobin levels; (f) use of Bifidobacterium lactis TY-S01 or its products in the preparation of drugs for improving pancreatic and / or liver damage caused by diabetes.

[0035] In some specific examples, in the above applications, the dosage form of the drug is tablets, powders, granules, capsules, emulsions, gels or liquid dosage forms.

[0036] It should be noted that the Bifidobacterium lactis TY-S01 or its culture, metabolites, bacterial suspension, bacterial powder or fermentation liquid in the present invention can be added with a pharmaceutically acceptable carrier to prepare different pharmaceutical dosage forms, such as tablets, powders, granules, capsules, emulsions, gels or liquid dosage forms; in addition, the preparation methods of pharmaceutically acceptable carriers and preparations are well known in the art and can be prepared differently according to clinical needs; in addition, the above-mentioned drugs, in addition to pharmaceutically acceptable carriers, can also include other pharmaceutically active ingredients for preventing or improving diabetes, and the pharmaceutically active ingredients can be chemically synthesized small molecules, natural small molecules, or biologically active ingredients such as polypeptides, which can be specifically selected according to those skilled in the art.

[0037] The embodiment of the present invention also provides an application of Bifidobacterium lactis TY-S01 or its product in preparing a health food, wherein the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the health food has one or more of the following functions: (a) helps maintain a healthy blood sugar level; (b) helps maintain a healthy blood lipid level; (c) helps to assist in protecting the pancreas and / or liver damage caused by diabetes; (d) helps to maintain a healthy insulin level.

[0038] It should be noted that the Bifidobacterium lactis TY-S01 or its culture, metabolite, bacterial suspension, bacterial powder or fermentation in the present invention can be prepared into a medicine for preventing or improving diabetes, and can also be prepared into a health product to help the body maintain a healthy state.

[0039] In some specific examples, in the above applications, the dosage form of the health food is tablets, powders, granules, capsules, emulsions, gels or liquid dosage forms.

[0040] It should be noted that Bifidobacterium lactis TY-S01 or its culture, metabolites, bacterial suspension, bacterial powder or fermentation can also be added with edible carriers and / or other edible ingredients to prepare health food, and the dosage form of the health food can also be tablets, powders, granules, capsules, emulsions, gels or liquid dosage forms; in addition, edible carriers and / or other edible ingredients are well known in the art and can be selected according to specific circumstances; for example, other edible ingredients can be prebiotics, other probiotics, dietary fiber, etc.

[0041] The embodiment of the present invention also provides an application of Bifidobacterium lactis TY-S01 or its product in preparing a functional food, wherein the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No.21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the functional food has one or more of the following functions: (a) helps maintain a healthy blood sugar level; (b) helps maintain a healthy blood lipid level; (c) helps to assist in protecting the pancreas and / or liver damage caused by diabetes; (d) helps to maintain a healthy insulin level.

[0042] It should be noted that Bifidobacterium lactis TY-S01 or its culture, metabolites, bacterial suspension, bacterial powder or fermentation can also be added with edible carriers and / or other edible ingredients to prepare functional foods, which can help the body maintain blood sugar, blood lipids and insulin at healthy levels through diet, and can also protect the pancreas and / or liver damage caused by diabetes.

[0043] In some specific examples, in the above applications, the functional food is a liquid food, a semi-solid food or a solid food.

[0044] It should be noted that the liquid food in the present invention includes juice-like beverages with high fluidity, such as probiotic beverages, and can also be liquid beverages with poor fluidity, such as yogurt; semi-solid food includes food with fluidity between solid food and liquid food, such as solid yogurt that can be eaten with a spoon; solid food includes granular, flaky or powdered food, such as probiotic biscuits, probiotic granules or probiotic instant powder, etc.

[0045] In order to better understand the present invention, the content of the present invention is further explained below in conjunction with specific examples, but the content of the present invention is not limited to the following examples.

[0046] In the following embodiments, Bifidobacterium lactis TY-S01 is derived from Chongqing Tianyou Dairy Co., Ltd. The strain is recorded in patent 202111569073.9. The strain is deposited in the General Microbiological Center of China Culture Collection Administration (CGMCC) with the deposit number CGMCC No.21255 and the deposit date of November 27, 2020.

[0047] 1. Cultivation and treatment of strains

[0048] Take the TY-S01 strain preserved in glycerol at -80°C, inoculate it into 5mL of MRS liquid culture medium supplemented with 0.05% cysteine ​​at a 2% inoculation rate, and culture it anaerobically at 37°C for 72h to activate the strain for 2 generations; centrifuge the activated bacterial solution at 4°C, 4000r / min for 10min, discard the supernatant, and collect the bacteria. Wash the bacteria with physiological saline, centrifuge again, repeat twice to obtain bacterial mud, add lyophilization protective agent, vacuum freeze-dry and freeze-dry to obtain bacterial powder, store it at -20°C, and use it for gavage in animal experiments. Before use, the TY-S01 bacterial powder was gradient diluted with physiological saline, and the number of live bacteria was counted by the plate count method. According to the counting results, the concentration of the bacterial solution was adjusted to 10 with physiological saline. 10 CFU / mL, and obtain the bacterial suspension for oral administration.

[0049] 2. Improvement of Bifidobacterium lactis TY-S01 on type 2 diabetes in mice

[0050] In the following experiments, the Bifidobacterium lactis TY-S01 used was deposited in the General Microbiological Center of China Microorganism Culture Collection Administration with the deposit number of CGMCC No.21255.

[0051] 1. Grouping and treatment of experimental animals

[0052] Thirty-two 5-week-old SPF-grade C57BL / 6J male mice were selected and housed in a standardized laboratory at room temperature of 25℃±2℃, relative humidity of 50%±5%, and 12h light / 12h dark. The experiment began after one week of adaptive feeding. After the adaptation period, the mice were randomly divided into a normal group, a model group, an acarbose group, and a TY-S01 group, with 8 mice in each group. The experimental period was 16 weeks, and the animals in each group had free access to water during the experiment. The normal group consumed ordinary feed, and the mice in the model group, acarbose group, and TY-S01 group were fed a high-fat diet (containing 34.9% fat, 1.3% carbohydrates, and 1.5% omega-3 fatty acids). The mice in the normal group were injected with sodium citrate buffer solution. After 1 week, the fasting blood glucose levels of the mice were measured, and the mice with blood glucose levels exceeding 11.1 mmol / L were considered as type 2 diabetic mice. Subsequently, the TY-S01 group was gavaged 10 times a day for 10 minutes. 10 The patients were treated with a suspension of Bifidobacterium lactis TY-S01 at a concentration of 100 CFU / kg·BW. The acarbose group was gavaged with 40 mg / kg·BW of acarbose solution every day, while the normal group and the model group were gavaged with 10 mL / kg·BW of normal saline every day for 9 weeks.

[0053] Body weight was measured once a week during the experiment, and food and water intake was recorded every two days during gavage. On the last day of the experiment, the mice were killed after fasting for 12 hours and measuring their fasting blood glucose. Blood samples were collected and centrifuged at 3000 rpm for 10 min at 4°C. The upper serum was taken and stored at -80°C for further analysis (serum index test). Tissue samples (pancreas and liver) were quickly removed and rinsed, and part of the tissue was fixed in 4% polyformaldehyde for 48 hours. The rest of the tissue was frozen in liquid nitrogen and then stored at -80°C.

[0054] (II) Different test situations

[0055] (1) Changes in body weight, food intake, and water intake of mice

[0056] The weight changes of mice in each group are as follows Figure 1 As shown in (A), the results showed that the body weight of mice in each group continued to increase in the first 5 weeks, with no significant difference between the groups; STZ was injected in the 7th week, and the body weight of all high-fat diet-fed groups (model group, acarbose group and TY-S01 group) decreased significantly in the 8th and 9th weeks; after the intervention of the drugs acarbose and Bifidobacterium lactis TY-S01, the weight loss of mice in the acarbose group and TY-S01 group was alleviated.

[0057] The final body weight (week 16) of each group of mice was as follows: Figure 1 As shown in (B), the results showed that the body weight of mice in the model group (20.24±2.83g) was significantly lower than that in the normal group (25.19±2.95g), while the body weight of mice in the acarbose group (23.94±1.43g) and the TY-S01 group (24.01±2.21g) was significantly increased compared with that of mice in the model group (p<0.05).

[0058] The average daily food intake of mice in each group is as follows Figure 1 As shown in (C), the results showed that during the entire treatment process, the average daily food intake of mice in the model group (10.93±1.62g) was significantly higher than that in the normal group (5.28±0.27g), while the average daily food intake of mice in the acarbose group (9.34±0.55g) and the average daily food intake of mice in the TY-S01 group (9.94±1.16g) were both reduced compared with the average daily food intake of mice in the model group (p>0.05).

[0059] The average daily water intake of mice in each group is as follows Figure 1As shown in (D), the results showed that during the entire treatment process, the average daily water intake of mice in the model group (13.21±2.41mL) was significantly higher than that in the normal group (6.90±0.71mL), while the average daily water intake of mice in the acarbose group (8.01±0.80mL) and the average daily water intake of mice in the TY-S01 group (9.94±1.17mL) were significantly reduced compared with the average daily water intake of mice in the model group (p<0.05).

[0060] The above results showed that Bifidobacterium lactis TY-S01 alleviated the diabetic characteristics of type 2 diabetic mice, and there was no significant difference in the effect with acarbose (p>0.05).

[0061] (2) Changes in fasting blood glucose in mice

[0062] At the end of the 7th week and the 16th week, the fasting blood glucose levels of mice in each group were tested using a Roche blood glucose meter (model: 929, purchased from Roche Diagnostics (Shanghai) Co., Ltd.). The results are shown in Table 1. Figure 2 As shown, the results showed that compared with the normal group, the fasting blood glucose levels of the other three groups of mice at the 7th week were significantly higher than those of the normal group (p<0.05), indicating that the type Ⅱ diabetes model was successfully established; after 9 weeks of treatment, the fasting blood glucose of the model group mice (18.49±3.44mmol / L) was still significantly higher than that of the normal group (4.13±0.69mmol / L), and compared with the model group, after 9 weeks of treatment, the fasting blood glucose levels of the acarbose group (7.24±2.88mmol / L) and the TY-S01 group (10.58±4.72mmol / L) were significantly decreased (p<0.05). The above results show that Bifidobacterium lactis TY-S01 has the effect of improving hyperglycemia in type Ⅱ diabetic mice, and there is no significant difference in the effect of acarbose (p>0.05).

[0063] (3) Oral glucose tolerance test

[0064] To detect glucose homeostasis, oral glucose tolerance test (OGTT) experiment was performed on mice in each group at week 16. The mice were fasted for 12 h and had free access to water. Then, 2 g / kg·BW glucose was gavaged into the stomach. Blood glucose levels were measured at 0, 30 min, 60 min, 90 min and 120 min using a Roche blood glucose meter (model: 929, purchased from Roche Diagnostics (Shanghai) Co., Ltd.). Blood glucose curves were drawn and the area under the curve (AUC) was calculated.

[0065] The results are as follows Figure 3 As shown in (A) and 3(B), the results showed that at the end of the 16th week, the study found that the glucose tolerance of type II diabetic mice was impaired, and the AUC of OGTT in the model group mice was more than 3 times that of the normal group. Figure 3(A, B). After treatment with Bifidobacterium lactis TY-S01, glucose tolerance levels were improved (p>0.05). The above results indicate that Bifidobacterium lactis TY-S01 has the potential to improve glucose tolerance in type II diabetic mice.

[0066] (4) Determination of serum indicators

[0067] In the following tests, an enzyme-linked immunosorbent assay kit (purchased from Shanghai Yuanju Biotechnology Center) was used to detect serum insulin and glycosylated hemoglobin A1c levels; the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula: HOMA-IR = fasting blood glucose (mmol / L) × fasting serum insulin (mIU / L) / 22.5; a fully automated analyzer (model: BS-460, purchased from Shenzhen Mindray Animal Medical Technology Co., Ltd.) was used to determine the levels of Glu, ALT, AST and TG in mouse serum.

[0068] 1) Serum insulin and HOMA-IR levels in mice

[0069] Insulin is secreted by pancreatic β cells and can control the synthesis and metabolism of carbohydrates in the body. Insulin resistance is one of the main pathogenesis of type 2 diabetes and can be assessed by HOMA-IR. Improving insulin resistance is a good way to treat diabetes.

[0070] The serum insulin level and HOMA-IR level of each group of mice were tested. Figure 4 (A) and Figure 4 As shown in (B), the results showed that the serum insulin and HOMA-IR levels of the model group mice were significantly higher than those of the normal group (p<0.05). Compared with the model group, the insulin and HOMA-IR levels were significantly reduced in the acarbose group and the TY-S01 group (p<0.05). The above results show that Bifidobacterium lactis TY-S01 can improve the serum insulin level of type II diabetic mice and reduce insulin resistance, and there is no significant difference in the effect of acarbose (p>0.05).

[0071] 2) Serum HbA1c and Glu levels in mice

[0072] Glycated hemoglobin is the product of the combination of hemoglobin in red blood cells in human blood and blood sugar. The combination of blood sugar and hemoglobin to form glycated hemoglobin is an irreversible reaction and is proportional to the blood sugar concentration. It can be maintained for about 120 days, so the glycated hemoglobin test can usually reflect the average blood sugar level in the past 8-12 weeks. Glycated hemoglobin is composed of HbA1a, HbA1b, and HbA1c, of which HbA1c accounts for about 70% and has a relatively stable structure. It is often used as a monitoring indicator for diabetes control in clinical practice.

[0073] The serum HbA1c and Glu levels of each group of mice were tested. Figure 5 and Figure 6 As shown, the results showed that the serum HbA1c and Glu levels of the model group mice were significantly higher than those of the normal group (p<0.05); compared with the model group, the acarbose group and the TY-S01 group significantly reduced the serum HbA1c and Glu levels of type II diabetic mice (p<0.05), and there was no significant difference in the drug effects of Bifidobacterium lactis TY-S01 and acarbose (p>0.05).

[0074] 3) Mouse serum TG levels

[0075] Triglyceride (TG) is an organic substance and a component of lipids. In normal plasma, TG maintains a dynamic equilibrium state. However, for diabetic patients, due to high blood sugar, the oxidation of sugar in mitochondria is relatively enhanced, which increases the synthesized cholesterol substances. Continuous high blood sugar will promote insulin-induced hepatic HMGCOA (3-hydroxy-3-methylglutaryl coenzyme A) reductase synthesis, thereby increasing cholesterol synthesis and causing serum TG levels to rise.

[0076] The serum TG levels of mice in each group were tested. Figure 7 As shown in the results, the serum TG level of mice in the model group was significantly higher than that in the normal group (p<0.05). Compared with the model group, the TG level was significantly reduced in the acarbose group and the TY-S01 group (p<0.05), and there was no significant difference in the drug effects of Bifidobacterium lactis TY-S01 and acarbose (p>0.05).

[0077] 4) Serum ALT and AST levels in mice

[0078] Serum ALT and AST levels are important indicators for evaluating liver function. When the liver is damaged, the permeability of the liver cell membrane increases, and ALT and AST are released into the blood.

[0079] The serum ALT and AST levels of mice in each group were tested. Figure 8 As shown in (A) and 8(B), the results showed that the serum ALT and AST levels of the model group mice were significantly higher than those of the normal group (p<0.05); compared with the model group, the serum ALT and AST levels of the acarbose group and the TY-S01 group were significantly reduced (p<0.05). The above results show that Bifidobacterium lactis TY-S01 has a protective effect on the liver of type II diabetic mice, and there is no significant difference between the drug effects of Bifidobacterium lactis TY-S01 and acarbose (p>0.05).

[0080] (5) Histological and pathological analysis

[0081] Mouse liver and pancreatic tissues were dehydrated in a series of ethanol solutions, embedded in paraffin, and cut into 4 μm thick sections; after dewaxing and dehydration, the sections were stained with hematoxylin and eosin (H&E) for morphological examination; the stained liver and pancreatic tissues were observed under an optical microscope, and images were taken for histopathological analysis.

[0082] 1) Pancreatic pathology analysis

[0083] Pancreatic sections were stained with H&E to evaluate the protective effect of Bifidobacterium lactis TY-S01 on pancreatic β-cell damage in diabetic mice. Fig. 9 As shown in the figure, the pancreatic tissue structure of mice in the normal group was intact, and the islet cells were normal in morphology and uniform in size. The pancreatic tissue of mice in the model group was severely damaged, the islets were significantly atrophied, the number of pancreatic β cells was significantly reduced compared with the normal group, and there were bleeding spots and inflammatory cell infiltration in the intercellular space; compared with the model group, acarbose and Bifidobacterium lactis TY-S01 intervention for 9 weeks can significantly alleviate the atrophy of the islets in type II diabetic mice, and reduce the apoptosis and cell damage of pancreatic β cells.

[0084] 2) Liver pathology analysis

[0085] Liver sections were stained with H&E to evaluate the protective effect of Bifidobacterium lactis TY-S01 on liver cell damage in type II diabetic mice. Fig.10 As shown, the results showed that the liver cell structure of the normal group mice was normal, the nuclear membrane was intact, the nucleolus was clearly visible, and there was no lipid droplet and inflammatory cell infiltration in the liver cytoplasm, while the liver cells of the model group mice showed severe damage such as necrosis, inflammatory cell infiltration and vacuolation; after the mice were gavaged with Bifidobacterium lactis TY-S01, the liver tissue hepatocytes were arranged more regularly and had normal morphology, and round vacuoles were visible in the cytoplasm of a small number of hepatocytes. In addition, the number of vacuoles in the liver tissue hepatocytes of the mice in the acarbose group was significantly reduced compared with the model group. The above results show that Bifidobacterium lactis TY-S01 can significantly improve the liver lesions of type II diabetic mice, and the improvement effect is not significantly different from that of acarbose.

[0086] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be covered by the scope of the claims of the present invention.

Claims

1. Use of Bifidobacterium lactis TY-S01 or its product in the preparation of a medicament for preventing, improving or treating diabetes, the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No.21255, and the product is a culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01.

2. The use according to claim 1, characterized in that: Diabetes is type 2 diabetes.

3. The use according to claim 2, characterized in that: Applications include one or more of the following: (a) Use of Bifidobacterium lactis TY-S01 or a product thereof in the preparation of a medicament for alleviating weight loss and / or increased water intake caused by diabetes; (b) Use of Bifidobacterium lactis TY-S01 or a product thereof in the preparation of a medicament for lowering blood sugar levels; (c) Use of Bifidobacterium lactis TY-S01 or a product thereof in the preparation of a medicament for lowering insulin levels; (d) Use of Bifidobacterium lactis TY-S01 or its product in the preparation of a medicament for reducing insulin resistance; (e) Use of Bifidobacterium lactis TY-S01 or its product in the preparation of a medicament for reducing the level of glycosylated hemoglobin; (f) Use of Bifidobacterium lactis TY-S01 or a product thereof in the preparation of a medicament for improving pancreatic and / or liver damage caused by diabetes.

4. The drug according to claim 1 or 2, characterized in that The drug is in the form of tablets, powders, granules, capsules, emulsions, gels or liquids.

5. Use of Bifidobacterium lactis TY-S01 or its products in the preparation of health food, the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No.21255, the product is the culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the health food has one or more of the following functions: (a) Helps maintain healthy blood sugar levels; (b) Helps maintain healthy blood lipid levels; (c) Helps protect the pancreas and / or liver from damage caused by diabetes; (d) Helps maintain healthy insulin levels.

6. The use according to claim 4, characterized in that: The dosage form of health food is tablets, powders, granules, capsules, emulsions, gels or liquids.

7. Use of Bifidobacterium lactis TY-S01 or its products in the preparation of functional foods, the preservation number of Bifidobacterium lactis TY-S01 is CGMCC No. 21255, the product is the culture, metabolite, bacterial suspension, bacterial powder or fermentation liquid of Bifidobacterium lactis TY-S01; the functional food has one or more of the following functions: (a) Helps maintain healthy blood sugar levels; (b) Helps maintain healthy blood lipid levels; (c) Helps protect the pancreas and / or liver from damage caused by diabetes; (d) Helps maintain healthy insulin levels.

8. The use according to claim 7, characterized in that: Functional foods are liquid foods, semi-solid foods or solid foods.

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