CN113827601A - Application of ursodeoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction - Google Patents
Application of ursodeoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction Download PDFInfo
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- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 title claims abstract description 34
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- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 3
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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Abstract
The invention provides application of bear deoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction. And feeding the ursodeoxycholic acid to the low-birth-weight piglet, wherein the low-birth-weight piglet is a suckling piglet. The bear deoxycholic acid provided by the invention can obviously improve the growth performance of the piglets with low birth weight caused by intrauterine growth restriction, improve the intestinal health of the piglets with low birth weight caused by intrauterine growth restriction, and provide a feasible scheme for solving the production problem of the piglets caused by intrauterine growth restriction.
Description
Technical Field
The invention belongs to the technical field of livestock raising, and particularly relates to application of bear deoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction.
Background
Intrauterine growth restriction (IUGR) results in low birth weight of piglets and secondary high mortality and low growth performance during lactation, which is one of the outstanding problems currently existing in the pig industry. According to statistics, the weight of about 15-20% of newborn piglets in China is lower than 1.1 kg. In the newborn period (1, 7, 21d), the absolute length, the weight, the relative length, the relative weight and the villus height of the jejunum of the IUGR piglet are all lower than those of a normal birth weight piglet, the intestinal villus of the IUGR piglet is shrunk and thinned, and the microvilli is rare; the expression of protein related to nutrient digestion, absorption and metabolism is reduced, the expression of protein related to oxidative stress and apoptosis is up-regulated, and the growth and development of the jejunum mucosa of IUGR piglets are damaged and have persistence, so that the expression of the protein related to absorption and metabolism is disturbed, the utilization efficiency of feed is further reduced, and the sustainable development of the pig industry in China is influenced. Therefore, the growth performance and intestinal health of the low-birth-weight piglets caused by IUGR are improved, and the method has great significance for ensuring the healthy and sustainable development of the pig industry in China.
Ursodeoxycholic acid (UDCA), chemical name 3a,7 beta-dihydroxy-5 beta-cholestane-24-acid, odorless and bitter. The medicine is used for increasing bile acid secretion, changing bile components, reducing cholesterol and cholesterol ester in bile, and being beneficial to gradually dissolving cholesterol in gallstone. However, no relevant report is available for the application of the ursodeoxycholic acid to the piglets with low birth weight caused by limited intrauterine growth.
Disclosure of Invention
The invention provides application of bear deoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction, and provides a feasible scheme for solving the production key problem of the piglets caused by intrauterine growth restriction.
Specifically, the invention provides the following technical scheme:
application of ursodeoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction is provided.
The inventor of the invention screens key bile acid molecules by comparing the difference of intestinal bile acid metabolism of the low-birth-weight piglets and the normal initial-weight piglets caused by intrauterine growth restriction, deeply researches the action and mechanism of the key bile acid molecules on the growth performance and intestinal health of the low-birth-weight piglets, and discovers that the ursodeoxycholic acid is a new nutrition regulation molecular target spot for improving the growth inhibition of the low-birth-weight piglets caused by intrauterine growth restriction. Experiments prove that the ursodeoxycholic acid is fed to the low-birth-weight piglets by a specific dosage, so that the growth performance of the piglets can be obviously improved, and the intestinal health of the piglets is improved.
Preferably, in the above application, the low-birth-weight piglet has a birth weight not higher than 0.95 kg.
Preferably, in the above application, the low-birth-weight piglet is a suckling piglet.
Preferably, in the application, the low-birth-weight piglet is a piglet aged 1-7 days.
Preferably, in the above application, the ursodeoxycholic acid is fed to the low-birth-weight piglet through oral feeding.
Further preferably, the feeding amount of the ursodeoxycholic acid is 40-60 mg per kg body weight per day.
Preferably, in the above application, the ursodeoxycholic acid is added into water to prepare a ursodeoxycholic acid solution to be fed to the low-birth-weight piglets.
Preferably, in the above application, the alleviating the growth inhibition of the low-birth-weight piglets caused by the intrauterine growth restriction is characterized by improving the growth performance of the low-birth-weight piglets caused by the intrauterine growth restriction.
Preferably, in the above application, the relieving of growth inhibition of low-birth-weight piglets due to intrauterine growth restriction is characterized by improving intestinal health of low-birth-weight piglets due to intrauterine growth restriction.
The invention has the following beneficial effects:
the bear deoxycholic acid provided by the invention can obviously improve the growth performance of the piglets with low birth weight caused by intrauterine growth restriction, improve the intestinal health of the piglets with low birth weight caused by intrauterine growth restriction, and provide a feasible scheme for solving the production problem of the piglets caused by intrauterine growth restriction.
Drawings
Fig. 1 is a comparison of piglet body weight in the UDCA treated group and the control group of example 1.
FIG. 2 is a representative micrograph of H & E staining and PAS staining of the UDCA treated group and the control group in example 1.
FIG. 3 shows a comparison of histological scores for H & E staining and PAS staining of the UDCA treated group and the control group in example 1.
FIG. 4 is a comparison of mRNA expression of the proinflammatory cytokine-related gene and the barrier function-related gene in colon tissue for the UDCA-treated group and the control group in example 1.
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 Effect of bear deoxycholic acid on alleviating growth inhibition of low-birth-weight piglets due to intrauterine growth restriction
1. And (3) experimental design: 10 multiparous sows (Changbai X Dabai) were selected and fed with corn-soybean meal type basal ration according to NRC standard (2012), and were allowed to drink water freely. The sow is naturally delivered on day 114 of gestation, and the piglets are born in 10 litters (Duroc is multiplied by Changbai is multiplied by Dabai, namely, the piglets are bred by Duroc boars and (Changbai is multiplied by Dabai) sows). Newborn piglet Birth Weight (BW) was recorded immediately at birth, and 2 low birth weight piglets (LBW, 0.75-0.95 kg) were selected from each litter and divided into 2 groups (n ═ 10) respectively. The control group was fed with 1mL of sterile saline per day, and the UDCA group was fed with 1mL of sterile saline solution containing UDCA dissolved therein (wherein the amount of UDCA used was 50mg/kg BW) per day for 7 days. Throughout the trial, administration of antibiotics or other drugs to sows and piglets was prohibited.
2. Collecting samples: weighing all piglets in the UDCA group and the control group on the 8 th day of the experimental period, randomly selecting 6 piglets (n is 6) from each group for slaughtering and sampling, separating out the colon, collecting the middle segment tissue sample of the colon, quickly freezing by liquid nitrogen, and storing at-80 ℃ for gene quantification and cytokine determination; in addition, a 2 cm-long colon middle section tissue sample is collected, fixed and stored by using a 4% paraformaldehyde solution and used for paraffin embedding, PAS staining and HE staining.
3. Results and analysis:
fig. 1 is a comparison of average weights of piglets in the UDCA-treated group and the control group in example 1, and after feeding UDCA for 7 days, the average weight of piglets in the UDCA-treated group was found to be significantly higher than that in the control group (P ═ 0.097).
Fig. 2 is a representative photomicrograph of the H & E staining and PAS staining of the UDCA treated and control groups of example 1, showing that the goblet cells were significantly more abundant than the control group, indicating increased mucin secretion in the colon of piglets after UDCA treatment, which is more beneficial to intestinal health.
Fig. 3 is a comparison of H & E staining and PAS staining of the UDCA treated and control groups of example 1 showing histological score comparison, and it can be seen that the UDCA treated group had a significantly lower score than the control group, indicating a reduced degree of damage to the colon of piglets after UDCA treatment.
FIG. 4 is a comparison of mRNA expression of the proinflammatory cytokine-related genes and the barrier function-related genes in colon tissue in the UDCA treated group and the control group in example 1, and it can be seen that the UDCA group significantly down-regulates the mRNA expression of the proinflammatory cytokine-related genes (IL-1. beta. and TNF-. alpha.), up-regulates the mRNA expression of the barrier function-related genes (ZO-1, OCLD, CLDN1, MUC1 and MUC2) and FXR (4D).
Note: the data results for histological scores and gene mRNA expression in fig. 3 and 4 are the sum and average of the data results for selected piglets in each group.
The results show that reasonable supplement of UDCA has obvious effects of improving growth performance and improving intestinal health of low-birth-weight piglets caused by intrauterine growth restriction.
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.
Claims (9)
1. Application of ursodeoxycholic acid in relieving growth inhibition of low-birth-weight piglets caused by intrauterine growth restriction is provided.
2. The use according to claim 1, wherein the low-birth-weight piglets have a birth weight of not more than 0.95 kg.
3. The use according to claim 1 or 2, wherein the low birth weight piglets are suckling piglets.
4. The use according to any one of claims 1 to 3, wherein the low birth weight piglets are 1 to 7 days old piglets.
5. The use of any one of claims 1 to 4, wherein said ursodeoxycholic acid is fed orally to said low-birth-weight piglet.
6. The use according to claim 5, wherein the ursodeoxycholic acid is fed in an amount of 40-60 mg per kg body weight per day.
7. The use of claim 5 or 6, wherein said ursodeoxycholic acid is added to water to prepare a ursodeoxycholic acid solution for feeding said low-birth-weight piglets.
8. The use according to any one of claims 1 to 7, wherein said alleviation of growth inhibition of low-birth-weight piglets due to intrauterine growth restriction is characterized by an improvement in the growth performance of low-birth-weight piglets due to intrauterine growth restriction.
9. The use of any one of claims 1-8, wherein said alleviating growth inhibition in low-birth-weight piglets due to restricted intrauterine growth is characterized by improving the intestinal health of low-birth-weight piglets due to restricted intrauterine growth.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2208497A1 (en) * | 2009-01-15 | 2010-07-21 | Charité-Universitätsmedizin Berlin (Charité) | Use of Ursodeoxycholic acid (UDCA) for enhancing the general health condition of a tumor patient |
| CN108783015A (en) * | 2018-07-09 | 2018-11-13 | 山东龙昌动物保健品有限公司 | Application of the bile acid in preparing the additive for improving Growth Performance of Weaning Piglets |
| CN109010347A (en) * | 2018-05-07 | 2018-12-18 | 华南农业大学 | Application of the chenodeoxycholic acid in terms of improving the damage of animal intestinal tract barrier function |
| CN112955149A (en) * | 2019-01-23 | 2021-06-11 | 沙裴隆有限公司 | Composition for preventing or treating inflammatory bowel disease comprising taurodeoxycholic acid or pharmaceutically acceptable salt thereof as active ingredient |
-
2021
- 2021-09-16 CN CN202111088909.3A patent/CN113827601A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2208497A1 (en) * | 2009-01-15 | 2010-07-21 | Charité-Universitätsmedizin Berlin (Charité) | Use of Ursodeoxycholic acid (UDCA) for enhancing the general health condition of a tumor patient |
| CN109010347A (en) * | 2018-05-07 | 2018-12-18 | 华南农业大学 | Application of the chenodeoxycholic acid in terms of improving the damage of animal intestinal tract barrier function |
| CN108783015A (en) * | 2018-07-09 | 2018-11-13 | 山东龙昌动物保健品有限公司 | Application of the bile acid in preparing the additive for improving Growth Performance of Weaning Piglets |
| CN112955149A (en) * | 2019-01-23 | 2021-06-11 | 沙裴隆有限公司 | Composition for preventing or treating inflammatory bowel disease comprising taurodeoxycholic acid or pharmaceutically acceptable salt thereof as active ingredient |
Non-Patent Citations (1)
| Title |
|---|
| 杨丽娟等: ""熊去氧胆酸防治极低出生体重儿胃肠外营养相关胆汁瘀积临床研究"", 《南京医科大学学报（自然科学版）》, vol. 31, no. 5, 31 May 2011 (2011-05-31), pages 758 - 760 * |
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