Method for improving liver function impairment caused by diabetes

Abstract

The invention discloses a method for improving liver function impairment caused by diabetes mellitus so as to improve liver function recovery and ensure that a proper amount of selenium and zinc are supplemented to an organism. According to the invention, a proper amount of selenium and zinc ion combined supplement is supplemented, so that the obvious effect of selenium and zinc ions on reversing the liver function of the diabetic mouse is defined, and the levels of ALT, AST and other enzymes in the serum of the diabetic mouse can be effectively reduced. The combined application of selenium and zinc ions provides a new potential way for the treatment of diabetic liver function impairment, is expected to be further developed and applied in the field of biological medicine, and provides a new thought and strategy for the prevention and treatment of diabetic complications.

Description

Technical Field

[0001] The present invention relates to the technical field of liver function health care, and in particular to a method for improving liver function damage caused by diabetes. Background Art

[0002] Diabetes is a global chronic metabolic disease with numerous complications that seriously affect the quality of life and health of patients. Among them, liver damage caused by diabetes is one of the more common and complex complications. The liver plays a key role in the metabolism of substances such as sugar, fat, and protein. Long-term hyperglycemia, insulin resistance and other factors in the diabetic state can lead to structural and functional abnormalities of liver cells, such as fatty degeneration, inflammatory response, liver fibrosis, etc., which in turn affect the normal metabolism, detoxification and synthesis functions of the liver.

[0003] Selenium is an important antioxidant that works in the form of selenium ions. Diabetic patients usually have high levels of oxidative stress in their bodies, which produces a large number of free radicals, which can damage structures such as biomembranes, proteins, and nucleic acids in liver cells. Selenium ions can remove free radicals through selenium-dependent enzymes such as glutathione peroxidase (GSH-Px). For example, GSH-Px can reduce harmful hydrogen peroxide to water, reduce the damage to the liver caused by oxidative stress, and thus help restore liver function. Selenium ions may be involved in regulating the insulin signaling pathway in the liver. Insulin can promote the uptake of glucose and glycogen synthesis by liver cells, and selenium ions can enhance insulin sensitivity to a certain extent. At the same time, in terms of lipid metabolism, selenium ions help regulate processes such as β-oxidation of fatty acids in the liver, reduce the accumulation of fat in the liver, and promote the recovery of liver function.

[0004] Zinc ions are important components of many enzymes, such as superoxide dismutase (SOD). In diabetic patients, oxidative stress occurs in the liver due to factors such as high blood sugar. SOD can catalyze superoxide anions and reduce the damage of free radicals to liver cells; in addition, zinc ions can regulate the activity of immune cells in the liver, remove harmful substances such as pathogens and immune complexes that enter the liver, and regulate inflammatory responses to avoid damage to the liver caused by excessive inflammation, which is beneficial to the recovery of liver function.

[0005] Although selenium and zinc are essential trace elements for the human body, excessive amounts of selenium and zinc ions can be toxic to the human body. During the treatment of diabetes, excessive supplementation of selenium ions can lead to selenium poisoning. For the liver, selenium poisoning can cause liver cell necrosis and liver damage. High concentrations of zinc ions can interfere with the normal metabolic balance of other metal ions (such as copper ions) in the liver, cause gastrointestinal discomfort, affect the absorption of other nutrients, and indirectly have a negative impact on the liver's nutrient supply and metabolism. Currently, commonly used zinc / selenium hypoglycemic drugs mainly focus on controlling blood sugar levels, but liver damage caused by diabetes and liver toxicity damage caused by long-term drug treatment cannot be well avoided, and the targeted treatment effect is not obvious. Summary of the invention

[0006] The present invention aims to solve the deficiencies in the prior art and provide a method for improving liver function damage caused by diabetes, so as to improve liver function recovery while ensuring that the body is supplemented with an appropriate amount of selenium and zinc.

[0007] To achieve the above object, the present invention is implemented according to the following technical solutions:

[0008] The present invention aims to provide a method for improving liver function damage caused by diabetes, comprising the following steps:

[0009] S1. Construction of diabetes model: C57BL / 6 mice were selected and the diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ);

[0010] S2. Grouping and treatment: After successful modeling, the mice were randomly divided into a diabetes group, a selenium-zinc ion combined treatment group, a normal control group, and an insulin treatment group. The mice in the selenium-zinc ion combined treatment group were gavaged with 200 μL of 100-150 μg / mL selenium-zinc ion solution per mouse, the diabetes group was given an equal amount of normal saline, and the insulin treatment group was given an intraperitoneal injection of 0.18 mg / kg insulin per day. The treatment was suspended after 13 weeks.

[0011] S3. Blood glucose monitoring of mice: Blood glucose monitoring began after adaptive feeding of mice throughout the treatment process. Treatment was suspended after 13 weeks, but blood glucose monitoring was not suspended.

[0012] S4. Blood biochemical test of liver function indicators: Collect blood from mice to test liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST);

[0013] S5. HE staining of liver: Mouse liver tissues were collected and HE staining was used to observe the liver cell morphology and the degree of fatty degeneration.

[0014] Beneficial effects:

[0015] 1. The present invention has clarified for the first time the significant effect of selenium and zinc ions in reversing the liver function of diabetic mice, and can effectively reduce the levels of enzymes such as ALT and AST in the serum of diabetic mice.

[0016] 2. The combined use of selenium and zinc ions in the present invention provides a new potential approach for the treatment of diabetic liver damage, and is expected to be further developed and applied in the field of biomedicine, providing new ideas and strategies for the prevention and treatment of diabetic complications. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a schematic diagram of the effect of combined use of selenium and zinc ions on glucose uptake in liver cells, where the control group is normal cells and IR is an insulin resistance cell model.

[0018] Figure 2 This is a schematic diagram of the effect of selenium ions on glucose uptake in liver cells, where the control group is normal cells and IR is an insulin resistance cell model.

[0019] Figure 3 This is a schematic diagram of the effect of zinc ions on glucose uptake in liver cells, where the control group is normal cells and IR is an insulin resistance cell model.

[0020] Figure 4 This is a schematic diagram of the changes in blood sugar in each group of mice after treatment, where a is the diabetes group, b is the selenium treatment group, c is the zinc treatment group, d is the selenium and zinc combined treatment group, and e is the insulin treatment group.

[0021] Figure 5 This is a schematic diagram of the changes in liver function indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in each group of mice after treatment, where a is the diabetes group, b is the selenium treatment group, c is the zinc treatment group, d is the selenium and zinc combined treatment group, and e is the insulin treatment group. The area below the dotted line indicates the normal value range of AST and ALT.

[0022] Figure 6 This is a schematic diagram of HE staining of the liver of each group of mice after treatment, where a is the normal control group, b is the diabetes group, c is the insulin treatment group, d is the selenium treatment group, e is the zinc treatment group, and f is the selenium-zinc combined treatment group. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0024] Example 1

[0025] (1) Construction of diabetes model: C57BL / 6 mice were selected and a diabetic mouse model was established by intraperitoneal injection of 100 mg / kg (based on mouse body weight) of streptozotocin (STZ). The diabetic model was considered to be successfully established when the random blood glucose level was greater than 16.7 mmol / L and the fasting blood glucose level was greater than 11.1 mmol / L;

[0026] (2) Grouping and treatment: After successful modeling, the mice were randomly divided into a diabetes group, a selenium-zinc ion combined treatment group, a normal control group, and an insulin treatment group. The mice in the selenium-zinc ion combined treatment group were gavaged with 200 μL of 62.5 μg / mL selenium-zinc ion solution per mouse, the diabetes group was given an equal amount of normal saline, and the insulin treatment group was given an intraperitoneal injection of 0.18 mg / kg insulin per day. The treatment was suspended after 13 weeks.

[0027] (3) Blood glucose monitoring of mice: Blood glucose monitoring began after adaptive feeding of mice throughout the treatment process. After 13 weeks, treatment was suspended but blood glucose monitoring was not suspended. Blood glucose was measured by blood glucose meter using tail vein blood samples at 9:00 a.m. every day.

[0028] (4) Blood biochemical detection of liver function indicators: Blood was collected from mice to detect liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST);

[0029] (5) Liver HE staining: Mouse liver tissues were collected and HE staining was used to observe liver cell morphology and the degree of fatty degeneration.

[0030] Example 2

[0031] The specific implementation of the single treatment of selenium and zinc is the same as that of Example 1, except that only the mice in the selenium ion treatment group are intragastrically administered with 200 μL of a 62.5 μg / mL selenium ion solution.

[0032] Example 3

[0033] The specific implementation of zinc treatment alone is the same as in Example 1, except that the mice in the zinc ion treatment group were intragastrically administered with 200 μL of 62.5 μg / mL zinc ion solution per mouse.

[0034] according to Figure 1 As shown, compared with the IR group, the simultaneous supplementation of selenium and zinc ions significantly reduced the glucose content in the supernatant and the glucose content was lower than that in the normal control group, indicating that selenium and zinc dual ions can produce a synergistic effect to jointly promote hepatocyte glucose uptake and the effect is far better than supplementing zinc or selenium ions alone.

[0035] according to Figure 2 As shown, compared with the IR group, selenium ion supplementation could significantly reduce the glucose content in the supernatant, indicating that the uptake of sugar into the liver cells increased.

[0036] according to Figure 3 As shown, compared with the IR group, zinc ion supplementation can also significantly reduce the glucose content in the supernatant, indicating that the hepatocytes uptake more sugar into the cells.

[0037] according to Figure 4 As shown in the figure, based on the monitoring of blood sugar changes in each group of mice, the blood sugar level of the selenium-zinc combined treatment group began to decline from the third week of treatment, and dropped to normal levels in the ninth week, and even remained within the normal range after stopping treatment. Although the blood sugar levels of the other groups also decreased, their blood sugar stability and hypoglycemic effect were not as good as those of the selenium-zinc combined treatment group, and they would rebound to varying degrees within a week after stopping treatment.

[0038] according to Figure 5 As shown in the data, by testing the liver function indicators ALT and AST of mice, the ALT and AST of the mice in the diabetic group were higher than the normal values, indicating severe liver damage. In comparison, the ALT and AST levels of several treatment groups decreased. In addition, the livers of mice using selenium or zinc alone were still in a highly damaged state, while the liver function of mice using the combined zinc and selenium group dropped to normal levels.

[0039] according to Figure 6 As shown in the figure, HE staining results of mouse liver showed that the morphological structure of liver cells in the normal group mice was normal, without obvious degeneration. Compared with the normal group, HE staining sections of the liver of the diabetic group mice showed obvious fatty degeneration symptoms such as large-area vacuoles and loose cytoplasm. With the intervention of selenium and zinc, the fatty vacuoles in the liver were significantly weakened, and the improvement effect of the selenium-zinc combined treatment group was more obvious. This shows that the combined treatment of selenium and zinc can effectively improve liver function.

[0040] The above-mentioned embodiments only express the implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the attached claims.

Claims

1. A method for improving liver function damage caused by diabetes, characterized in that The following steps are involved: S1. Construction of diabetes model: C57BL / 6 mice were selected and the diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ); S2. Grouping and treatment: After successful modeling, the mice were randomly divided into a diabetes group, a selenium-zinc ion combined treatment group, a normal control group, and an insulin treatment group. The mice in the selenium-zinc ion combined treatment group were gavaged with 200 μL of 100-150 μg / mL selenium-zinc ion solution per mouse, the diabetes group was given an equal amount of normal saline, and the insulin treatment group was given an intraperitoneal injection of 0.18 mg / kg insulin per day. The treatment was suspended after 13 weeks. S3. Blood glucose monitoring of mice: Blood glucose monitoring began after adaptive feeding of mice throughout the treatment process. Treatment was suspended after 13 weeks, but blood glucose monitoring was not suspended. S4. Blood biochemical test of liver function indicators: Collect blood from mice to test liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST); S5. HE staining of liver: Mouse liver tissues were collected and HE staining was used to observe the liver cell morphology and the degree of fatty degeneration.

2. The improvement method according to claim 1, characterized in that: The following steps are involved: (1) Construction of diabetes model: C57BL / 6 mice were selected and a diabetic mouse model was established by intraperitoneal injection of 100 mg / kg (based on mouse body weight) of streptozotocin (STZ). The diabetic model was considered to be successfully established when the random blood glucose level was greater than 16.7 mmol / L and the fasting blood glucose level was greater than 11.1 mmol / L; (2) Grouping and treatment: After successful modeling, the mice were randomly divided into a diabetes group, a selenium-zinc ion combined treatment group, a normal control group, and an insulin treatment group. The mice in the selenium-zinc ion combined treatment group were gavaged with 200 μL of 62.5 μg / mL selenium-zinc ion solution per mouse, the diabetes group was given an equal amount of normal saline, and the insulin treatment group was given an intraperitoneal injection of 0.18 mg / kg insulin per day. The treatment was suspended after 13 weeks. (3) Blood glucose monitoring of mice: Blood glucose monitoring began after adaptive feeding of mice throughout the treatment process. After 13 weeks, treatment was suspended but blood glucose monitoring was not suspended. Blood glucose was measured by blood glucose meter using tail vein blood samples at 9:00 a.m. every day. (4) Blood biochemical detection of liver function indicators: Blood was collected from mice to detect liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (5) Liver HE staining: Mouse liver tissues were collected and HE staining was used to observe liver cell morphology and the degree of fatty degeneration.

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