阅读说明：本技术 一种缓解脂多糖所致肉鸡生长抑制的饲料添加剂及其应用 (Feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide and application thereof ) 是由 朴香淑 龙沈飞 马嘉瑜 王剑 刘苏捷 贺腾飞 于 2021-08-31 设计创作，主要内容包括：本发明提供一种缓解脂多糖所致肉鸡生长抑制的饲料添加剂及其应用。所述饲料添加剂包含：富马酸、山梨酸、柠檬酸、苹果酸、百里香酚、香兰素和丁香酚。该饲料添加剂能减少脂多糖攻毒后肉鸡体重损失,降低脂多糖攻毒后肉鸡血清总胆固醇、二胺氧化酶、干扰素-γ含量,增加血清过氧化氢酶含量,为解决肉鸡因脂多糖引发的生产问题提供可行性方案。(The invention provides a feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide and application thereof. The feed additive comprises: fumaric acid, sorbic acid, citric acid, malic acid, thymol, vanillin and eugenol. The feed additive can reduce the weight loss of the broiler chickens after the lipopolysaccharide is attacked, reduce the contents of total cholesterol, diamine oxidase and interferon-gamma in the serum of the broiler chickens after the lipopolysaccharide is attacked, increase the content of catalase in the serum, and provide a feasible scheme for solving the production problem of the broiler chickens caused by the lipopolysaccharide.)

1. A feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide is characterized by comprising: fumaric acid, sorbic acid, citric acid, malic acid, thymol, vanillin and eugenol.

2. The feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide according to claim 1, which comprises the following components in parts by weight: 14-18 parts of fumaric acid, 6-10 parts of sorbic acid, 5-9 parts of citric acid, 5-9 parts of malic acid, 0.5-2 parts of thymol, 0.2-0.6 part of vanillin and 0.02-0.06 part of eugenol.

3. The feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide according to claim 2, which comprises the following components in parts by weight: 16 parts of fumaric acid, 8 parts of sorbic acid, 7 parts of citric acid, 7 parts of malic acid, 1 part of thymol, 0.4 part of vanillin and 0.04 part of eugenol.

4. Use of a feed additive according to any one of claims 1 to 3 in the preparation of a feed or veterinary medicament.

5. The use of claim 4, wherein the feed or veterinary drug is a feed or veterinary drug for reducing weight loss of broiler chickens after lipopolysaccharide challenge.

6. The use of claim 4 or 5, wherein the feed or veterinary drug is a feed or veterinary drug for reducing the total cholesterol content of the serum of the broiler chickens after lipopolysaccharide challenge.

7. The use of any one of claims 4 to 6, wherein the feed or veterinary drug is a feed or veterinary drug for increasing the levels of catalase in the serum of broiler chicken after lipopolysaccharide challenge and the height of villi in jejunum, and reducing the levels of diamine oxidase, interferon-gamma and tumor necrosis factor-alpha.

8. A broiler feed comprising a basal feed and the feed additive of any one of claims 1-3.

9. The broiler feed of claim 8, wherein the amount of said feed additive added is 80-120 mg/kg basal feed, preferably 100mg/kg basal feed.

10. The broiler feed of claim 8 or 9, wherein the formula of said basal feed is as follows in weight percent: 61.74-65.17% of corn, 24.5-28.5% of soybean meal, 3.29-3.33% of fish meal, 2.90-3.81% of soybean oil, 1.20-1.30% of calcium hydrophosphate, 1.10-1.28% of stone powder, 0.30% of salt, 0.05-0.15% of DL-methionine, 0.04% of L-threonine and 0.50% of broiler premix;

wherein, each kg of the premix for the broiler chickens contains: vitamin a, 11,000 IU; vitamin D, 3,025 IU; vitamin E, 22 mg; vitamin K₃2.2 mg; thiamine, 1.65 mg; riboflavin, 6.6 mg; pyridoxine, 3.3 mg; cobalamin, 17.6 micrograms; nicotinic acid, 22 mg; pantothenic acid, 13.2 mg; folic acid, 0.33 mg; biotin, 88 μ g; choline chloride, 500 mg; iron, 48 mg; zinc, 96.6 mg; manganese, 101.76 mg; copper, 10 mg; selenium, 0.05 mg; iodine, 0.96 mg; 0.3 mg of cobalt.

Technical Field

The invention belongs to the technical field of feed additives, and particularly relates to a feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide and application thereof.

Background

Acute phase reactions are key reactions to infection or injury, affecting growth performance and metabolism. This systemic stress response may lead to the initiation of many behavioral and endocrine changes, increased production of free radicals, and decreased production parameters.

Lipopolysaccharide is a cell wall component of gram-negative bacteria, and can cause acute phase reactions and cause inflammation, disease and decreased production parameters of broiler chickens. At present, new high-efficiency feed additives for relieving growth inhibition of broilers caused by lipopolysaccharide are increasingly paid attention by stockbreeding workers.

The invention CN112042830A discloses a broiler feed additive and an application thereof. The broiler feed additive comprises plant essential oil and/or organic acid; wherein the plant essential oil comprises thymol and carvacrol, and the organic acid comprises benzoic acid, calcium formate and fumaric acid. The broiler feed additive provided by the invention CN112042830A can replace antibiotics, and improve broiler growth and anti-stress capability. However, no research report about whether the broiler chicken feed additive compounded by the plant essential oil and the organic acid can help to relieve broiler chicken growth inhibition caused by inflammatory injury reaction caused by lipopolysaccharide exists at present.

Disclosure of Invention

The invention provides a feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide and application thereof, and provides a feasible scheme for solving the key production problem of broiler chickens caused by lipopolysaccharide.

Specifically, the invention provides the following technical scheme:

a feed additive for alleviating growth inhibition of broilers caused by lipopolysaccharide comprises: fumaric acid, sorbic acid, citric acid, malic acid, thymol, vanillin and eugenol.

In the feed additive provided by the invention, the organic acid adopts components of fumaric acid, sorbic acid, citric acid and malic acid, so that the pH value of the gastrointestinal tract can be reduced, the intestinal microbial flora structure is improved, and the growth performance of livestock and poultry is obviously improved. The plant essential oil adopts the combination of thymol, vanillin and eugenol, has hydrophobic groups, can be combined with different action targets on bacterial cells to permeate into cell membranes and mitochondria of bacteria, divides lipids on the cell membranes and the mitochondria of pathogenic bacteria, enhances the permeability of the cells, causes the exosmosis of cell contents, and finally kills the pathogenic bacteria cells. Furthermore, thymol, vanillin and eugenol have synergistic effect, so that the expression of proinflammatory cytokines can be obviously reduced, and the inflammatory reaction of an organism caused by bacterial infection is relieved. Experiments prove that the feed additive compounded by the specific organic acid and the specific plant essential oil can obviously reduce the weight loss of the broiler chickens after the lipopolysaccharide is attacked, reduce the contents of total cholesterol, diamine oxidase and interferon-gamma in the serum of the broiler chickens after the lipopolysaccharide is attacked, and increase the content of catalase in the serum.

Preferably, the feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide comprises the following components in parts by weight: 14-18 parts of fumaric acid, 6-10 parts of sorbic acid, 5-9 parts of citric acid, 5-9 parts of malic acid, 0.5-2 parts of thymol, 0.2-0.6 part of vanillin and 0.02-0.06 part of eugenol.

Preferably, the feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide comprises the following components in parts by weight: 16 parts of fumaric acid, 8 parts of sorbic acid, 7 parts of citric acid, 7 parts of malic acid, 1 part of thymol, 0.4 part of vanillin and 0.04 part of eugenol.

The invention also provides application of the feed additive in preparation of feed or veterinary drugs.

Preferably, in the application, the feed or veterinary drug is a feed or veterinary drug for reducing weight loss of the broiler chickens after lipopolysaccharide challenge.

Preferably, in the application, the feed or veterinary drug is the feed or veterinary drug for reducing the total cholesterol content of the serum of the broiler chickens after the lipopolysaccharide challenge.

Preferably, in the application, the feed or veterinary drug is the feed or veterinary drug for improving the content of catalase in the serum of the broiler chicken after the lipopolysaccharide challenge and the height of villi in jejunum and reducing the content of diamine oxidase, interferon-gamma and tumor necrosis factor-alpha.

The invention also provides a broiler feed which comprises a basic feed and the feed additive provided by the invention.

Preferably, in the broiler feed provided by the invention, the addition amount of the feed additive is 80-120 mg/kg of basic feed, and more preferably 100mg/kg of basic feed.

Preferably, in the broiler feed provided by the invention, the formula of the basic feed comprises the following components in percentage by weight: 61.74-65.17% of corn, 24.5-28.5% of soybean meal, 3.29-3.33% of fish meal, 2.90-3.81% of soybean oil, 1.20-1.30% of calcium hydrophosphate, 1.10-1.28% of stone powder, 0.30% of salt, 0.05-0.15% of DL-methionine, 0.04% of L-threonine and 0.50% of broiler premix;

wherein, each kg of the premix for the broiler chickens contains: vitamin a, 11,000 IU; vitamin D, 3,025 IU; vitamin E, 22 mg; vitamin K₃2.2 mg; thiamine, 1.65 mg; riboflavin, 6.6 mg; pyridoxine, 3.3 mg; cobalamin, 17.6 micrograms; nicotinic acid, 22 mg; pantothenic acid, 13.2 mg; folic acid, 0.33 mg; biotin, 88 μ g; choline chloride, 500 mg; iron, 48 mg; zinc, 96.6 mg; manganese, 101.76 mg; copper, 10 mg; selenium, 0.05 mg; iodine, 0.96 mg; 0.3 mg of cobalt.

The invention has the following beneficial effects:

the feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide can obviously reduce weight loss of broiler chickens after lipopolysaccharide challenge, reduce the contents of total cholesterol, diamine oxidase and interferon-gamma in broiler chickens serum after lipopolysaccharide challenge, increase the content of serum catalase, and provide a feasible scheme for solving the production problem of broiler chickens caused by lipopolysaccharide.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications.

In the following examples, the equipment and the like used are not shown to manufacturers, and are all conventional products available from regular vendors. The process is conventional unless otherwise specified, and the starting materials used are commercially available from published sources.

Example 1

A feed additive for relieving growth inhibition of broiler chickens caused by lipopolysaccharide comprises the following components in parts by weight: 16 parts of fumaric acid, 8 parts of sorbic acid, 7 parts of citric acid, 7 parts of malic acid, 1 part of thymol, 0.4 part of vanillin and 0.04 part of eugenol.

Test examples

84 Aijia Yijia (AA) broilers selected in the test are randomly divided into 2 treatment groups (a control group and an experimental group), each treatment group comprises 7 repeating groups, and each repeating group comprises 6 chickens. Wherein:

control group: feeding basal diet, injecting lipopolysaccharide (3mg/kgBW) into abdominal cavity on day 42;

test group, feeding basal diet +100mg/kg feed additive, injecting lipopolysaccharide injection (3mg/kg BW) in abdominal cavity on 42 days;

all diets were fed as a powder. Randomly selecting one broiler chicken in each repeating group, weighing in the morning of 42 days, injecting lipopolysaccharide into the abdominal cavity, weighing again 24 hours after lipopolysaccharide injection, and slaughtering. Blood (8mL) was collected into a 10mL blood collection tube, and serum was obtained by centrifugation at 1,500 Xg for 15 minutes and stored at-80 ℃. Samples of duodenum, jejunum and ileum were taken for intestinal morphology detection.

In this experiment, Escherichia coli-derived lipopolysaccharide (L2880, serotype O55: B5) was purchased from Sigma-Aldrich.

The experimental basal diet was formulated with reference to NRC (1994), and the specific formulation is shown in table 1. Wherein, each kg of broiler premix contains: vitamin a, 11,000 IU; vitamin D, 3,025 IU; vitamin E, 22 mg; vitamin K₃2.2 mg; thiamine, 1.65 mg; riboflavin, 6.6 mg; pyridoxine, 3.3 mg; cobalamin, 17.6 micrograms; nicotinic acid, 22 mg; pantothenic acid, 13.2 mg; folic acid, 0.33 mg; biotin, 88 μ g; choline chloride, 500 mg; iron, 48 mg; zinc, 96.6 mg; manganese, 101.76 mg; copper, 10 mg; selenium, 0.05 mg; iodine, 0.96 mg; 0.3 mg of cobalt.

TABLE 1 composition and nutritional ingredients of basal diets (%, feeding base)

Raw materials	Earlier stage (d1-d21)	Late stage (d22-d42)
			Corn (corn)	61.74	65.17
Bean pulp	28.50	24.50
			Fish meal	3.29	3.33
Soybean oil	2.90	3.81
			Calcium hydrogen phosphate	1.30	1.20
Stone powder	1.28	1.10
			Salt	0.30	0.30
DL-methionine	0.15	0.05
			L-threonine	0.04	0.04
Premix compound	0.50	0.50
			Nutritional levels
Metabolic energy, kcal/kg	3051	3150
			Crude protein	20.68	19.06
Calcium carbonate	1.02	0.91
			Digestible phosphorus	0.43	0.40
Standard ileal digestible lysine	0.80	0.72
			Standard ileal digestible methionine	0.27	0.25
Standard ileal digestible threonine	0.58	0.53

Table 2 shows the influence of the organic acid and essential oil compound on the broiler body loss after lipopolysaccharide challenge, and the results show that the organic acid and essential oil compound can significantly reduce the broiler body weight loss after lipopolysaccharide challenge (P < 0.01).

TABLE 2 Effect of organic acid and essential oil complexes on broiler body loss after lipopolysaccharide challenge

Item	Control group	Test group	Standard error of mean	P value
					Body loss, g	40.33	27.50	2.63	<0.01

Note: the data results for the control combination test groups in the tables of the invention are the sum and average of the data results for the selected broilers in each replicate group.

Table 3 shows the influence of the organic acid and essential oil compound on the biochemical indexes of the serum of broilers subjected to lipopolysaccharide challenge, and the results show that the total cholesterol content of the serum of broilers in the test group is remarkably reduced (P is less than 0.05) after the lipopolysaccharide challenge.

TABLE 3 influence of organic acid and essential oil compounds on biochemical indexes of broiler serum after lipopolysaccharide challenge

Item	Control group	Test group	Standard error of mean	P value
					Glucose, mmol/L	15.13	14.82	0.33	0.52
Total Cholesterol, mmol/L	2.61	2.17	0.12	0.03
					Total protein, g/L	20.09	19.65	1.04	0.77

Table 4 shows the influence of the organic acid and essential oil compound on the antioxidant index of broilers after lipopolysaccharide challenge, and the results show that after lipopolysaccharide challenge, the serum catalase content of broilers in the test group is significantly increased (P is less than or equal to 0.05), and the content of duodenal superoxide dismutase and the content of ileal catalase are increased (P is 0.08).

TABLE 4 influence of organic acid and essential oil complexes on antioxidant index of broilers after lipopolysaccharide challenge

Table 5 shows that the influence of the organic acid and essential oil compound on the immune globulin in the serum of the broiler chickens after the lipopolysaccharide challenge, and the results show that the immune globulin in the serum of the broiler chickens after the lipopolysaccharide challenge has no statistical difference in each group.

TABLE 5 influence of organic acid and essential oil complexes on immune globulin in broiler serum after lipopolysaccharide challenge

Item	Control group	Test group	Standard error of mean	P value
					Immunoglobulin A, ug/mL	14.97	14.56	0.63	0.66
Immunoglobulin G, ng/L	10.57	10.50	0.48	0.92
					Immunoglobulin M, ug/mL	3.00	2.58	0.20	0.18

Table 6 shows the influence of the organic acid and essential oil compound on immune cytokines in the serum of broilers after lipopolysaccharide challenge, and the results show that after lipopolysaccharide challenge, the contents of diamine oxidase and interferon-r in the serum of broilers in the test group are significantly reduced (P is less than 0.05), and the tumor necrosis factor-alpha tends to be reduced (P is 0.07).

TABLE 6 influence of organic acid and essential oil complexes on immune cytokines in serum of broilers after lipopolysaccharide challenge

Table 7 shows the influence of the organic acid and essential oil compound on the intestinal morphology of broilers after lipopolysaccharide challenge, and the results show that the jejunal villi height of broilers in the test group is remarkably increased (P <0.05) after lipopolysaccharide challenge.

TABLE 7 influence of organic acid and essential oil complexes on intestinal morphology of broilers after lipopolysaccharide challenge

Item	Control group	Test group	Standard error of mean	P value
					Duodenum
Height of pile, μm	1361.73	1197.71	111.29	0.32
					Depth of crypt, μm	166.97	188.74	14.32	0.31
Villus height/crypt depth	8.14	6.62	0.69	0.15
					Jejunum
Height of pile, μm	824.07	1002.67	54.3	0.04
					Depth of crypt, μm	149.54	187.56	14.74	0.10
Villus height/crypt depth	5.61	5.56	0.55	0.95
					Ileum
Height of pile, μm	933.85	817.46	117.85	0.50
					Depth of crypt, μm	150.17	157.74	11.75	0.66
Villus height/crypt depth	6.11	5.27	0.59	0.34

The results show that the feed additive provided by the invention can obviously reduce the weight loss of the broiler chickens after the lipopolysaccharide is attacked, reduce the contents of total cholesterol, diamine oxidase and interferon-gamma in the serum of the broiler chickens after the lipopolysaccharide is attacked and increase the content of catalase in the serum, thereby providing a feasible scheme for solving the production problem of the broiler chickens caused by the lipopolysaccharide.

Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.