Application of dihydromyricetin and selenium composition in preparation of medicine for treating chicken fatty liver hemorrhagic syndrome

Abstract

The invention discloses application of a dihydromyricetin and selenium composition in preparation of a medicine for treating chicken fatty liver hemorrhagic syndrome, and belongs to the technical field of medicine for animal husbandry. The application of the dihydromyricetin and selenium composition in the preparation of the medicine for treating the chicken fatty liver hemorrhagic syndrome is found in the invention; the mass ratio of the dihydromyricetin to the selenium is (1-5g): (50-100mu g); the selenium is derived from selenium-enriched spirulina powder; the composition of dihydromyricetin and selenium is added into a chicken basal feed for application. The addition amount of the dihydromyricetin in the chicken basal feed is 1-5g / kg, and the addition amount of the selenium in the chicken basal feed is 50-100mu g / kg. The combined action of dihydromyricetin and selenium can significantly relieve the chicken fatty liver hemorrhagic syndrome and laying rate reduction in the late laying period of the Xinghua chicken; a new medicine choice is provided for treating the chicken fatty liver hemorrhagic syndrome in the laying hen breeding process and prolonging the laying period of laying hens.

Description

Technical Field

[0001] The invention belongs to the technical field of animal husbandry medicines, and in particular relates to application of a composition of dihydromyricetin and selenium in preparing a medicine for treating chicken fatty liver hemorrhagic syndrome. Background Art

[0002] Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional metabolic disease characterized by lipid metabolism disorders, liver rupture and hepatic hemorrhage. It is the most common non-infectious cause of death in laying hens around the world. The specific pathogenesis has not yet been determined. The widely accepted theory is the "two-hit theory". The first level of hit refers to the excessive deposition of triglycerides in the liver, which inhibits fatty acid oxidation and disrupts lipid metabolism in the liver; the second level of hit refers to the production of a large amount of reactive oxygen in the liver due to oxidative stress and insulin resistance, causing inflammation in the body and ultimately causing fatty liver hemorrhagic syndrome. FLHS will reduce the production performance of laying hens and the quality of eggs. At the same time, excessive lipid accumulation causes fatty degeneration of liver cells and leads to massive hepatic hemorrhage, which leads to various health problems and even causes the death of laying hens. At present, the main breeding method of the laying hen industry is the cage system. As one of the three largest egg-producing countries, more than 90% of my country's egg production comes from caged hens. Compared with traditional free-range laying hens, caged laying hens may have a higher chance of suffering from fatty liver hemorrhagic syndrome due to restricted activities. FLHS can cause a sharp drop in egg production and lead to non-infectious deaths in caged laying hens, imposing a huge economic burden on the laying hen industry.

[0003] Dihydromyricetin (DHM) is a polyphenolic hydroxydihydroflavanol and the main extract of the edible and medicinal plant rattan tea. As the flavonoid compound with the highest content in rattan tea, its specific structure is as follows: Figure 1 As shown in Figure 2, its polyhydroxy structure determines that it is easily oxidized by free radicals in the body, which has an adverse effect on its functional effects. In addition, DHM has poor solubility and is only soluble in hot water and ethanol. Its solubility in cold water at 25°C is only 0.2-0.32 mg / ml. The efficacy of DHM is affected by its bioavailability. Animal experimental data show that the bioavailability of DHM in rats is 4.02% (Liu and Wang 2017), which indicates that the bioavailability of DHM is poor. The main metabolic sites of DHM are in the liver and gastrointestinal tract, and part of it is absorbed by the blood. After being absorbed by the blood, DHM can be distributed throughout the body. In summary, the unstable chemical properties and low bioavailability of DHM greatly limit the pharmacology and clinical application of DHM.

[0004] Selenium (Se) is an essential micronutrient for humans and animals. As the active center of selenoenzymes and selenoproteins, it plays an important role in the energy metabolism and gene expression of organisms. Selenium is a component of more than 30 different selenoproteins, including glutathione peroxidase (GSH-Px), thioredoxin reductase (TrxR) or selenoprotein P (SelP). Selenium is involved in regulating oxidative stress, redox state and key cellular processes in almost all tissues and cell types. In nature, selenium mainly exists in inorganic form, such as sodium selenite and sodium selenate. Inorganic selenium is highly toxic, has low biological activity, and is not easily absorbed and utilized by the human body. Organic selenium can show higher bioavailability, such as selenomethionine (SeMet), selenocysteine ​​(SeCys) and selenium-enriched yeast (Selenium enriched yeast), Selenium rich spirulina (Se-SP), etc., because it is easily absorbed by the human digestive tract and has a higher toxicity threshold compared to organic forms.

[0005] Spirulina (Spirulina platensis) is cultivated in water, and its enrichment of inorganic selenium can be controlled by changing the cultivation conditions to form selenium-enriched spirulina. The addition of selenium and the rich biological active ingredients of spirulina can make the active functions of selenium-enriched spirulina particularly diverse and significant, including anti-oxidation, anti-cancer, promotion of liver tissue regeneration, immune regulation and other aspects.

[0006] At present, chicken fatty liver hemorrhagic syndrome has brought great adverse effects on livestock and poultry production and breeding. However, there is still no clear treatment plan for chicken fatty liver hemorrhagic syndrome. Summary of the invention

[0007] The embodiment of the present invention provides a dihydromyricetin and selenium composition for use in preparing a drug for treating chicken fatty liver hemorrhagic syndrome, aiming to solve the problem that there is still no clear therapeutic drug and treatment plan for chicken fatty liver hemorrhagic syndrome.

[0008] The technical solution of the present invention is achieved in this way:

[0009] The composition of dihydromyricetin and selenium is used in preparing medicine for treating chicken fatty liver hemorrhagic syndrome.

[0010] Preferably, in the composition of dihydromyricetin and selenium, the mass ratio of dihydromyricetin to selenium is 1-5 g:50-100 μg. More preferably, the mass ratio of dihydromyricetin to selenium is 2 g:50 μg.

[0011] Preferably, the selenium comes from selenium-enriched Spirulina powder.

[0012] Preferably, the selenium content in the selenium-enriched Spirulina powder is 20-160 μg / g. More preferably, the selenium content in the selenium-enriched Spirulina powder is 87.26 μg / g.

[0013] The above-mentioned dihydromyricetin and selenium composition is used in the preparation of a medicine for treating chicken fatty liver hemorrhagic syndrome, specifically by adding the dihydromyricetin and selenium composition to a basic chicken feed.

[0014] Preferably, the amount of dihydromyricetin added to the chicken basal feed is 1-5 g / kg, and the amount of selenium added to the chicken basal feed is 50-100 μg / kg; the chicken basal feed is used as the measurement base of the addition amount. More preferably, the amount of dihydromyricetin added to the chicken basal feed is 2 g / kg, and the amount of selenium added to the chicken basal feed is 50 μg / kg.

[0015] Preferably, the chicken basic feed comprises the following components in parts by weight:

[0016]

[0017] The premix provides the following essential ingredients per kilogram: vitamin A-10 KIU, vitamin B1-3 mg, vitamin B2-6.8 mg, vitamin B6-7 mg, vitamin B12-0.6 mg, vitamin D3 -5 KIU, vitamin E4-5 mg, vitamin K3-1.1 mg, biotin 0.28 mg, folic acid 1.6 mg, niacinamide 40 mg, calcium pantothenate 10 mg, choline chloride 360 ​​mg, zinc 60 mg, copper 17 mg, manganese 100 mg, iron 100 mg, iodine 1.3 mg, methionine 1.2 g, and methionine 1.2 g.

[0018] Preferably, the chicken in the present invention is a commonly raised chicken breed; more preferably, the chicken is Xinhua chicken.

[0019] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0020] Dihydromyricetin is a flavonoid compound extracted from rattan tea. Although the material is easy to obtain, its polyhydroxy chemical structure determines that its chemical properties are unstable, and it has the disadvantage of low bioavailability; selenium, as a necessary trace element for the body, has strong antioxidant properties and can effectively remove free radicals from the body. In the present invention, by forming a combination of dihydromyricetin and selenium (derived from selenium-rich spirulina algae powder), not only the problems of unstable chemical properties and low bioavailability of dihydromyricetin are alleviated by the presence of selenium, but also the synergistic effect of the combination of dihydromyricetin and selenium has a significant therapeutic effect on chicken fatty liver hemorrhagic syndrome, and is used in the preparation of a medicine for treating chicken fatty liver hemorrhagic syndrome.

[0021] In summary, the dihydromyricetin and selenium (derived from selenium-rich spirulina powder) in the present invention can significantly alleviate chicken fatty liver hemorrhagic syndrome and decreased egg production rate in Xinhua chickens in the late egg-laying period. In addition, the dihydromyricetin extracted from rattan tea and the selenium from selenium-rich spirulina powder are both natural products with no toxic side effects, providing a new drug option for treating chicken fatty liver hemorrhagic syndrome and prolonging the egg-laying cycle of laying hens during laying hen breeding. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is the chemical structural formula of dihydromyricetin.

[0023] Figure 2 The effect diagram of Se enhancing DHM in relieving fatty liver in laying hens in the example; wherein: (A) is the characterization of fatty liver hemorrhagic syndrome in laying hens caused by Xinhua chickens fed with ordinary feed, and the liver phenotype, HE staining and Oil Red O staining results are shown. (B) is the liver phenotype result diagram of laying hens in the Control group, DHM group and DHM+SeSP group. (C) is the HE staining result diagram of the three groups of laying hens. (D) is the Oil Red O staining result diagram of the three groups of laying hens. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. In addition, if there are descriptions of "first", "second", etc. in the embodiments of the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes, and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" can explicitly or implicitly include at least one of the features. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in this field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0025] At present, there is still no clear treatment drug and treatment plan for chicken fatty liver hemorrhagic syndrome. In order to solve the above technical problems, the present invention proposes a composition of dihydromyricetin and selenium for use in preparing a drug for treating chicken fatty liver hemorrhagic syndrome.

[0026] The experimental animals, tissues and reagents used in this example are:

[0027] The experimental chickens were 45-week-old Xinhua chickens, which were randomly divided into groups after 5 weeks of adaptive feeding. The liver and serum of Xinhua chickens were taken as experimental samples.

[0028] Dihydromyricetin: purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., purity>97%.

[0029] Selenium-enriched Spirulina: purchased from the Institute of Hydrobiology, Chinese Academy of Sciences. The Se content in selenium-enriched Spirulina powder reaches 87.26 μg / g.

[0030] The basic feed composition for Xinhua chickens is shown in Table 1.

[0031] Table 1 Basic feed composition for Xinhua chickens

[0032]

[0033] Note: The premix provides the following essential ingredients per kg: Vitamin A - 10 KIU, Vitamin B1 - 3 mg, Vitamin B2 - 6.8 mg, Vitamin B6 - 7 mg, Vitamin B12 - 0.6 mg, Vitamin D3 - 5 KIU, Vitamin E4 - 5 mg, Vitamin K3 - 1.1 mg, Biotin 0.28 mg, Folic acid 1.6 mg, Nicotinamide 40 mg, Calcium pantothenate 10 mg, Choline chloride 360 ​​mg, Zinc 60 mg, Copper 17 mg, Manganese 100 mg, Iron 100 mg, Iodine 1.3 mg, Methionine 1.2 g, Methionine 1.2 g.

[0034] Example 1

[0035] In this example, Xinhua chickens were selected as the production application objects and divided into a control group (Control group), a DHM group (2g / kg DHM group) and a DHM+SeSP group (2g / kg DHM+50ug / kg Se group). Egg production rate monitoring and H&E staining, Oil Red O staining, TG content detection and other experimental methods were performed to explore whether the effects of Se and DHM can successfully alleviate the disadvantage of a rapid decline in egg production rate in Xinhua chickens in the late egg production period, and to explore the relationship between its occurrence factors and fatty liver hemorrhagic syndrome in laying hens.

[0036] 1.1 Experimental groups and treatments

[0037] Forty-five Xinhua chickens aged 50 weeks were randomly divided into three groups, with five replicates in each group. The three groups were: Control group, DHM group, and DHM+SeSP group. The Control group was fed with a basic feed every day, and 50 g of grain was added at 9 am and 5 pm respectively, and the daily feed intake and egg production were recorded. The DHM group needed to add 2 g / kg dihydromyricetin to the ordinary feed, and the specific feeding method was the same as the Control. The DHM+SeSP group needed to add 2 g / kg dihydromyricetin and 50 ug / kg selenium (added by adding selenium-enriched spirulina powder with a Se content of 87.26 μg / g) to the ordinary feed, and the specific feeding method was the same as the Control group. After 7 weeks of continuous feeding, the Xinhua chickens were killed, and fresh liver samples were obtained, weighed, and frozen.

[0038] 1.2DHM and Se significantly increased the egg production rate of laying hens

[0039] By recording the number of eggs laid by Xinhua chickens every day, we obtained a table of egg production rate changes, and by weighing and recording the feed consumed and eggs laid every day, we obtained a table of feed-egg ratio changes. The results showed that the egg production rate of the laying hens in the Control group decreased week by week, and began to be lower than 60% in the 5th week, showing that the egg production performance decreased too quickly in the late egg production period. The egg production rate of the laying hens in the DHM group decreased relatively slowly. The egg production rate of the laying hens in the DHM+SeSP group was not only significantly higher than that of the Control group, but also still showed a high egg production rate in the 7th week, which was basically maintained at about 70%, significantly alleviating the disadvantage of the egg production performance of laying hens decreasing too quickly in the late egg production period (as shown in Table 2 Table of Egg Production Rate Changes of Xinhua Chickens).

[0040] The above results show that adding 2g / kg DHM to the diet can alleviate the decline in egg production rate in laying hens in the late egg-laying period, and supplementing 50ug / kg Se can significantly improve the effect of DHM, which is manifested by a significant increase in egg production rate in the late egg-laying period.

[0041] Table 2 Changes in egg production rate of Xinhua chickens

[0042]

[0043] Note: Egg production rate = total number of eggs laid in a cycle / number of days in a cycle / number of laying hens. In this experiment, 7 days is considered as one cycle.

[0044] (p<0.05)

[0045] 1.3Se enhances the effect of DHM in alleviating fatty liver hemorrhagic syndrome in laying hens

[0046] Since Xinhua chickens' egg-laying fatigue was greatly alleviated, it was speculated whether the possible factors were related to chicken fatty liver hemorrhagic syndrome. By photographing the liver phenotype of Xinhua chickens, it was found that the control group clearly showed the characteristics of laying hen fatty liver hemorrhagic syndrome, which was manifested by yellowing of the liver, greasy feeling to the touch, brittle texture, and even flake hemorrhage, which was consistent with the characteristics of laying hen fatty liver hemorrhagic syndrome (such as Figure 2 As shown in A). In addition, HE and Oil Red O staining of some liver tissues also showed fatty changes: HE staining showed lipid droplet vacuoles arranged around the central vein of the liver, disordered arrangement of liver cells, unclear boundaries of liver cords, etc.; Oil Red O staining showed obvious red-stained lipid droplets. The above results showed that laying hens had obvious fatty liver hemorrhagic syndrome.

[0047] By adding DHM and SeSP to the diet, it was found that the phenotype of fatty liver hemorrhagic syndrome in Xinhua chickens was significantly alleviated compared with the control group. The DHM+SESP group had the best effect in alleviating fatty liver. The liver was basically not yellow and had no bleeding symptoms, showing the dark red color that the liver should have (such as Figure 2HE staining results showed that a small amount of lipid droplet vacuoles were still visible in the DHM group, but there were almost no vacuoles in the DHM+SESP group, and the hepatic cords were arranged neatly and orderly (as shown in Figure 2). Figure 2 C). The results of Oil Red 0 were basically consistent with those of HE staining. In the DHM group, only a small area of ​​lipid droplets around the central vein were stained red, and in the DHM+SESP group, there was almost no red staining (as shown in Figure 2). Figure 2 D).

[0048] In addition, by testing the liver damage indicators AST and ALT in the serum of Xinhua chickens, it was found that both the DHM group and the DHM+SeSP group could alleviate the liver damage caused by chicken fatty liver hemorrhagic syndrome (as shown in Table 3), while reducing the triglyceride content in serum and liver and reducing lipid accumulation. Among them, the laying hens in the DHM+SeSP group showed significant differences compared with the Control group.

[0049] The above results indicate that the significant decrease in egg production in the Control group may be due to the fact that laying hens suffer from fatty liver hemorrhagic syndrome. At the same time, adding DHM to the diet at a concentration of 2g / kg can significantly alleviate fatty liver hemorrhagic syndrome in laying hens, and supplementing SeSP at a concentration of 50μg / kg can significantly improve the alleviating effect of DHM.

[0050] Table 3 Liver damage and intrahepatic lipid deposition

[0051]

[0052] (p<0.05)

[0053] Effect of 1.4Se on enhancing DHM to improve antioxidant capacity of laying hens

[0054] By analyzing the antioxidant indicators MDA, T-SOD activity and GSH-Px content in the serum and liver of Xinhua chickens, it was found that the MDA content and GSH-Px activity of the DHM group were significantly better than those of the Control group, while the DHM+SeSP group was significantly better than the DHM group, indicating that supplementing 50ug / kg selenium in the diet can significantly improve the effect of DHM on the antioxidant capacity of laying hens (as shown in Table 4).

[0055] Table 4 Oxidative damage to laying hens

[0056]

[0057]

[0058] (p<0.05)

[0059] Preliminary research in our laboratory found that the egg production rate of laying hens decreases rapidly in the later stage of laying. In order to explore the specific reasons and prolong their peak egg-laying period, we selected local chickens - Xinhua laying hens as the research objects, and divided them into ordinary feed group, DHM group, and DHM+SeSP group for experiments. The research results showed that adding DHM and SeSP to the diet can significantly relieve laying fatigue of laying hens, and thus found that the possible factor is that it alleviates fatty liver syndrome of laying hens by improving the body's antioxidant capacity, thereby improving the economic value of laying hens.

[0060] The experimental results show that:

[0061] 2g / kg DHM can effectively relieve laying fatigue in Xinhua chickens in the late laying period, that is, slow down the rapid decline in egg production rate; supplementing Se at a concentration of 50μg / kg can significantly improve the relief effect of DHM, and appropriately extend the laying period of laying hens, maintaining the egg production rate at around 70%. The laying hens in the Control group showed the characteristics of chicken fatty liver hemorrhagic syndrome, while 2g / kg DHM can significantly alleviate chicken fatty liver hemorrhagic syndrome, and supplementing Se at a concentration of 50μg / kg can significantly improve the effect of DHM, which is manifested by significantly reducing the accumulation of fat droplets and TG content in the liver, while reducing AST and ALT content. In addition, the laying hens in the Control group showed high antioxidant indicators, while the DHM+SeSP group significantly alleviated the oxidative damage of laying hens, which was manifested by significantly increasing GSH-Px activity and reducing MDA content.

[0062] In summary, adding 2g / kg DHM to the basic feed of chickens can alleviate the decline in egg production rate and fatty liver hemorrhagic syndrome in Xinhua laying hens in the late laying period, reduce lipid accumulation in the liver, and improve the body's antioxidant capacity. Supplementing 50ug / kg Se can significantly improve the effect of DHM.

[0063] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. The composition of dihydromyricetin and selenium is used in the preparation of a medicine for treating chicken fatty liver hemorrhagic syndrome.

2. The composition of dihydromyricetin and selenium according to claim 1 is used in the preparation of a drug for treating chicken fatty liver hemorrhagic syndrome, characterized in that: In the composition of dihydromyricetin and selenium, the mass ratio of the dihydromyricetin to the selenium is 1-5 g:50-100 μg.

3. The composition of dihydromyricetin and selenium according to claim 1 is used in the preparation of a drug for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The mass ratio of dihydromyricetin to selenium is 2g:50μg.

4. The composition of dihydromyricetin and selenium according to claim 1 is used in the preparation of a drug for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The selenium comes from selenium-rich spirulina powder.

5. The composition of dihydromyricetin and selenium according to claim 4 is used in the preparation of a drug for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The selenium content in the selenium-enriched spirulina powder is 20-160 μg / g.

6. The composition of dihydromyricetin and selenium according to claim 1 is used in the preparation of a drug for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The composition of dihydromyricetin and selenium is added into basic feed of chicken for application.

7. The use of the composition of dihydromyricetin and selenium according to claim 6 in the preparation of a medicament for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The amount of dihydromyricetin added to the chicken basic feed is 1-5 g / kg, and the amount of selenium added to the chicken basic feed is 50-100 μg / kg.

8. The use of the composition of dihydromyricetin and selenium according to claim 6 in the preparation of a medicament for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The amount of dihydromyricetin added to the chicken basic feed is 2 g / kg, and the amount of selenium added to the chicken basic feed is 50 μg / kg.

9. Use of the composition of dihydromyricetin and selenium according to claim 6 in the preparation of a medicament for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The chicken basic feed comprises the following components in parts by weight:

10. Use of the composition of dihydromyricetin and selenium according to claim 9 in the preparation of a medicament for treating chicken fatty liver hemorrhagic syndrome, characterized in that: The premix provides the following essential ingredients per kilogram: vitamin A-10 KIU, vitamin B1-3 mg, vitamin B2-6.8 mg, vitamin B6-7 mg, vitamin B12-0.6 mg, vitamin D3-5 KIU, vitamin E4-5 mg, vitamin K3-1.1 mg, biotin 0.28 mg, folic acid 1.6 mg, niacinamide 40 mg, calcium pantothenate 10 mg, choline chloride 360 ​​mg, zinc 60 mg, copper 17 mg, manganese 100 mg, iron 100 mg, iodine 1.3 mg, methionine 1.2 g, and methionine 1.2 g.

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