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Effect And Mechanism Of Glycyrrhetinic Acid On Growth In Neonatal Pigs

Posted on:2008-07-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z S HeFull Text:PDF
GTID:1103360242965744Subject:Clinical Veterinary Medicine
Abstract/Summary:PDF Full Text Request
Liquorice (Radix et Rhizoma Glycyrrhizae), the root or root together with the rhizome of legume such as Glycyrrhiza uralensis Fisch., Glycyrrhiza inflat Bat. and Glycyrrhiza glabra L., is deemed possessing the effects of invigorating spleen, replenishing qi, eliminating phlegm, arresting cough, clearing away heat and toxins, relieving spasm and pain, and moderating the properties of other drugs and so on. In modern pharmacology, it is illustrated that Glycyrrhetinic Acid (GA) represents one of the main constituents of licorice and has many therapeutic properties, including antiinflammatory, antiulcer, antiallergic, antiviral, hepaprotective, antitumour, immumodulating actions. Because its molecular structure is similar to cortisol's, GA inhibits the activity of 11β-hydroxysteroid dehydrogenase type 2, thus retards the transformation and enhances the function of cortisol, and is often clinically used as substitute of the latter. It is authenticated in recent years that glucocorticoid enhances the growth in neonatal pigs. For example, administration of dexamethasone at birth promotes the growth of piglets, and cortisol promotes development of small intestine and endogenous synthesis of arginine in enterocytes of neonatal pigs. Because arginme in sow's milk is deficient, its endogenous synthesis in piglets has physiological significance. However, compared with 1- to 3-d-old pigs, both blood cortisol and endogenous synthesis of arginine declined markedly in 7- to 21-d-old suckling pigs, thus submaximal growth is manifested. Increasing arginine availability is an effective way to enhance growth in suckling piglets.In view of the cognition that glucocorticoid enhances the growth and endogenous synthesis of arginine in neonatal pigs, and that GA exhibits glucocorticoid-like and other multiple properties, and that, especially, little is known about GA on the growth and arginine nutrition in those pigs, this present study investigated the effects of GA on the growth in sow-reared 7- to 21-d-old and early-weaned piglets fed with milk-replacing diet, and the effects and mechanism of GA on the endocrine, plasma arginine concentration, hematology, blood biochemical indices and volatile fatty acid concentration, viscera development, activity of omithine decarboxylase in small intestine mucosa of piglets, and in vitro lymphocytes proliferation. ExperimentⅠEffects of glycyrrhetinic acid (GA) on the growth in suckling piglets. The effects of oral administration of GA on the growth in suckling piglets were investigated by screening out the suitable among the different doses of GA and comparing with cortisol. Twenty 7-d-old Duroc×Landrace×Yorkshire suckling piglets were randomly assigned to one of four treatments (5 pigs per group) on the body weight (BW) and sex basis, received oral administration of GA by 25, 50, 100 mg·pig-1 or saline (control) respectively, and reared within original litter. The BW at 7-, 14-, 21-d-old, and average daily gain (ADG), weight gain rate (WGR) were determined. The results showed that, the ADG, WGR of the group infusion GA of 100 mg·pig-1 were the highest in all of the treatments. Thirty-six 7-d-old piglets were randomly assigned to one of three treatments (12 pigs per group) on the BW and sex basis, received oral administration of cortisol 10 mg·kg-1 BW (Cortisol group), GA 40 mg·kg-1 BW (GA group) and saline (control) respectively. The indices were determined as former. The ADG of GA group were higher (P<0.05) than the control during 7- to 14-d-old and 7- to 21-d-old, and more (P<0.05) than the Cortisol group during 14- to 21-d-old. The WGR of GA group were higher (P<0.1) than the cortisol group during 7- to 21-d-old, and the BW of GA group was more (P<0.1) than the control at 21-d-old. The ADG of cortisol group were increased (P>0.05) during 7- to 14-d-old and 7- to 21-d-old, decreased (P>0.05) during 14- to 21-d-old. It is indicated that the oral administration of GA at 40 mg·kg-1 BW for 3 d during 7- to 9-d-old enhanced the growth in suckling 7- to 21-d-old piglets while cortisol at 10 mg·kg-1 BW did not affect it significantly.ExperimentⅡEffects of GA on the growth in early-weaned piglets and screening out the suitable dose added in the milk-replacing powder (MRP) for piglet. 7-d-old Landrace×Yorkshire male pigs were fed with milk freshly prepared by MRP and water as basic diet. After 2 d adaptive period, twenty pigs were randomly assigned to one of four treatments (1 pig/pen, 5 pigs/group) according to BW and litter. MRP contained GA of 0, 100, 200, 400 mg·kg-1 respectively for 12 d. The BW at 9-, 14-, 21-d-old, and the growth performance, diarrhea frequency during those period, and hematology indices at 14-, 21-d-old were determined to screen out the suitable dose of GA added in the MRP. The results showed that, the BW of the group GA at 200 mg·kg-1 were the highest at 14- and 21-d-old, and the ADG, WGR, and average daily feed intake (ADFI) most, and diarrhea frequency least during 9- to 14-d-old, 14- to 21-d-old and 9- to 21-d-old, and the feed/gain least during 9- to 14-d-old among all groups (P>0.05). The white blood cells (WBC) of the group GA at 400 mg·kg-1 were the most among all groups, the lymphocytes (LYM) more than the control (P<0.05), and the monocytes more than the control and the group GA at 100 mg·kg-1 (P<0.05), at 14-d-old. The monocytes of group GA at 400 mg·kg-1 were less than the 100 mg·kg-1 (P<0.05), and the ratios of LYM to leucocytes of group 200 mg·kg-1 were more than the 100 mg·kg-1 (P<0.05), at 21-d-old. It is indicated that GA added in MRP affected the growth performance, diarrhea frequency and blood white cell count in the piglets. Compared with the others, the dose of GA at 200 mg·kg-1 was suitable.ExperimentⅢEffects of glycyrrhetinic acid (GA) on the plasma hormone and amino acid level and hematology indices in early-weaned piglets. 7-d-old Landrace×Yorkshire male pigs were weaned and fed with milk prepared by MRP and water as basic diet. After 2 d adaptation period, thirty pigs were randomly assigned to one of two groups on the basis of body weight and litter (15 pigs/group). The MRP contained GA of 200 mg·kg-1 for 12 d as GA group, basic diet as control. At 9-, 14-, 21-d-old, the body weight and growth performance in the period were measured and blood of 8 pigs randomly picked in each group was sampled from anterior vena cava for analysis of plasma amino acid. The plasma hormone level and hematology indices of 6 pigs randomly picked in each group were determined at 14- and 21-d-old. The results showed that, compared with the control, the ADG, WGR, ADFI and average daily arginine intake (ADAI) of GA group were increased (P<0.05), and the ratios of feed to gain (F/G) decreased (P<0.05), during 9- to 14-d-old, and the ADG was increased (P=0.05), F/G decreased (P<0.05) during 9- to 21-d-old. The plasma concentration of arginine was higher (P<0.05), and glucagon content, less (P<0.05), at 21-d-old than the control. The blood percentage of lymphocyte to leukocyte were increased (P<0.05) while that of neutrophil to leukocyte was decreased at 14- and 21-d-old, and the mean corpuscular hemoglobin concentration increased (P<0.05) at 14-d-old; the mean corpuscular volume were elevated (P<0.05), the ratios of neutrophil to lymphocyte lessened (P<0.05), at 21-d-old, compared with the control. It is indicated that added GA of 200 mg·kg-1 in MRP promoted the growth of early-weaned piglets, increased endogenous synthesis of arginine and haemopoiesis, regulated endocrine and immunity.ExperimentⅣThe in vitro effects of GA on lymphocyte proliferation in piglets. The lymphocytes extracted from 7-, 14-, and 21-d-old pigs' peripheral blood were cultured and the in vitro effect of glycyrrhetinic acid (GA, at 100 mg·L-1 and a series of five fold dilution) on the lymphocyte proliferation with or without Concannvalin A (ConA) was determined by MTT method. The results showed that, compared with the control, the A570 values at 100 mg·L-1 GA were least (P<0.05 or P<0.01) among all groups; and the A570 values of GA groups at concentration less than 100 mg·L-1 were not different from the control (P>0.05). The A570 values of GA plus ConA groups at all GA concentration were lower (P<0.05 or P<0.01) than the control in 7- and 14-d-old pig's lymphocytes and only at 100 mg·L-1 GA less than the control in 21-d-old pigs' lymphocytes. It is indicated that, the lymphocyte proliferation in vitro was restrained with GA at 100 mg·L-1, and yet not enhanced with GA at less than the concentration. The effects of GA on lymphocyte proliferation in vitro induced by ConA were diverse in lymphocytes extracted from different age pigs.ExperimentⅤEffects of GA on blood biochemical composition and volatile fatty acid (VFA) of piglets. 7-d-old Landrace×Yorkshire male pigs were weaned and fed with milk prepared by MRP and water as basic diet. After 2 d adaptation period, 12 pigs were randomly assigned to one of two groups (1 pig/pen, 6 pigs/group). The basic diet as control, GA group were fed with MRP contained GA 200 mg·kg-1 for 12 d. The average daily feed intake (ADFI), crude protein, crude fat and arginine intake (ADAI) were measured. The blood was obtained from anterior vena cava for analysis of biochemical composition and volatile fatty acid at 14- and 21-d-old. The results showed that, compared with the control, the concentration of metacetonic acid and isovaleric acid of GA group were increased (P<0.05) at 14-d-old; metacetonic acid was increased (P<0.05), butyric acid and isovaleric acid were decreased (P<0.05) at 21-d-old. The blood urea, ammonia, glucose, total protein, albumin, total cholesterin did not differ (P>0.05). It is indicated that added GA 200 mg·kg-1 in MRP affected the metabolism of fat in early-weaned piglets.ExperimentⅥEffects of GA on viscera development of early-weaned piglets. 7-d-old Landrace×Yorkshire male pigs were weaned and fed with milk prepared by MRP and water as basic diet. After 2 days adaptation period, 12 pigs were randomly assigned to one of two groups (1 pig/pen, 6 pigs/group). The basic diet as control, the MRP contained GA 200 mg·kg-1 for 12 d as GA group. At 21-d-old, the pigs were weighed and killed, and the viscera mass and index (viscera mass/BW) were measured; the protein content in small intestine mucosa and the ornithine decarboxylase (ODC) activity in enterocytes of jejunum was determined. The villus, crypt and lamina propria of jejunum and ileum were measured post-paraffin section with hematoxylin-eosin stain. The results showed that, compared with the control, the liver index and small intestine mass/length of GA group were increased (P<0.05); the villus of jejunum and ileum, the crypt of ileum, and the ODC activity in enterocytes of jejunum were enhanced (P<0.05). It is indicated that added GA 200 mg·kg-1 in MRP boosted the liver and small intestine development of pigs, and increased the villus of jejunum and ileum and crypt of ileum and the ODC activity of enterocytes.
Keywords/Search Tags:glycyrrhetinic acid, neonatal pigs, growth, pharmacological effect, mechanism
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