Role Of Lung SIRT1 In Broilers With Ascites Syndrome And The Therapeutic Mechanism Of Compound Traditional Chinese Medicine

Ascites syndrome(AS)is a metabolic syndrome,hypoxia is the main causes of AS.The main pathological process of AS includes pulmonary arterial hypertension(PAH),heart failure(HF).SIRT1 provides protection in hypoxia and is a therapeutic target for diseases such as PAH and HF.The results showed that lung tissue injury and respiratory function were impaired in AS,the compound traditional Chinese medicines(CTCM)used in our research group could improve pulmonary vascular endothelial function and alleviate liver fibrosis in AS.In this experiment,the changes of SIRT1 and its related factors in lung tissue of broilers with AS were detected to study the pathogenesis of AS and the prevention and therapeutic effects of CTCM.Method and result 300 Ross308 broilers were randomly divided into five groups,blank group was bred with basal feed,model group was bred with mixed feed(9-11℃,added 3% lard and 4% fish meal to basal feed,added 0.12% Na Cl to drinking water),CTCM high and low dose group(on the basis of model group respectively given a dose of 2,1m L·(kg·d)-1 CTCM in drinking water),L-Arg group(on the basis of model group added a dose of 1% L-Arg to mixed feed).Observe the clinical symptoms of broilers,at 35 days old,10 broilers were randomly selected from each group,organ necropsy changes and lung histopathological changes were observed,the relative expression of SIRT1,Bcl-2 and Bax m RNA in lung tissue were detected by quantitative real-time PCR,the contents of SIRT1,PGC-1α,Bcl-2 and Bax proteins in lung tissue were detected by ELISA,the T-SOD activity in serum were detected by xanthine oxidase,MDA content in serum were detected by thiobarbituric acid.The main results of the test are as follows: 1.Broilers with AS are slow response,depressed,fewer or none diet,feather mess,abdominal swelling,cyanotic skin,and labored breathing;a large amount of transparent yellow liquid in the abdominal cavity;right ventricular wall is thin,soft,and dilated;pulmonary congestion,edema;hepatomegaly and yellow deposits on liver surface;some broilers kidney are hyperemic and white deposits on the surface.lung tissue of broilers with AS structure loose,thickened membrane,parabronchial dilatation or stenosis,smooth muscle layer atrophy,red blood cell exudation in the lumen,pulmonary capillary atrophy,stenosis,rupture,pulmonary arteriolysis,endothelial cell shedding,smooth muscle arrangement disorder,adventitial hyperplasia and light staining.2.At 35 days of age,compared with the blank group,the relative expression of SIRT1 m RNA in lung tissue of broilers in the model group decreased significantly(P<0.01);compared with the model group,the relative expression of SIRT1 m RNA in lung tissue of broilers in the CTCM high and low dose groups increased significantly(P<0.01),the relative expression of SIRT1 m RNA in lung tissue of broilers in the LArg group increased significantly(P<0.01).3.At 35 days of age,compared with the blank group,the relative expression of Bcl-2 m RNA in lung tissue of broilers in the model group decreased significantly(P<0.01);compared with the model group,the relative expression of Bcl-2 m RNA in lung tissue of broilers in the CTCM high and low dose groups increased significantly(P<0.01),the relative expression of Bcl-2 m RNA in lung tissue of broilers in the L-Arg group increased significantly(P<0.01).4.At 35 days of age,compared with the blank group,the relative expression of Bax m RNA in lung tissue of broilers in the model group increased significantly(P<0.01);compared with the model group,the relative expression of Bax m RNA in lung tissue of broilers in the CTCM high and low dose groups decreased significantly(P<0.01),the relative expression of Bax m RNA in lung tissue of broilers in the L-Arg group decreased significantly(P<0.01).5.At 35 days of age,compared with the blank group,the contents of SIRT1 protein in lung tissue of broilers in the model group decreased significantly(P<0.01);compared with the model group,the contents of SIRT1 protein in lung tissue of broilers in the CTCM high and low dose groups increased significantly(P<0.01),the contents of SIRT1 protein in lung tissue of broilers in the L-Arg group increased significantly(P<0.01).6.At 35 days of age,compared with the blank group,the contents of PGC-1α protein in lung tissue of broilers in the model group decreased significantly(P<0.01);compared with the model group,the contents of PGC-1α protein in lung tissue of broilers in the CTCM high and low dose groups increased significantly (P<0.01 or P<0.05),the contents of PGC-1α protein in lung tissue of broilers in the L-Arg group increased significantly(P<0.05).7.At 35 days of age,compared with the blank group,the contents of Bcl-2 protein in lung tissue of broilers in the model group decreased significantly(P<0.01);compared with the model group,the contents of Bcl-2 protein in lung tissue of broilers in the CTCM high and low dose groups increased significantly(P<0.01),the contents of Bcl-2 protein in lung tissue of broilers in the L-Arg group increased significantly(P<0.05).8.At 35 days of age,compared with the blank group,the contents of Bax protein in lung tissue of broilers in the model group increased significantly(P<0.01);compared with the model group,the contents of Bax protein in lung tissue of broilers in the CTCM high and low dose groups decreased significantly(P<0.01 or P<0.05),the L-Arg group have no significant difference.9.At 35 days of age,compared with the blank group,the T-SOD activity in serum of broilers in the model group decreased significantly(P<0.01),the contents of MDA in serum of broilers in the model group increased significantly;compared with the model group,the T-SOD activity in serum of broilers in the CTCM high and low dose groups increased significantly(P<0.01),the contents of MDA in serum of broilers in the CTCM high and low dose groups decreased significantly(P<0.01),the T-SOD activity in serum of broilers in the L-Arg group increased significantly(P<0.05),the contents of MDA in serum of broilers in the L-Arg group decreased significantly(P<0.05).Conclusion 1.The regulation of abnormal cell apoptosis and lower antioxidant capacity regulated by decreased expression of SIRT1 in the lung tissue of broilers with ascites syndrome induced lung injury,which was involved in the pathogenesis and development of ascites syndrome.2.The compound traditional Chinese medicines of Astragalus membranaceus,Angelica sinensis,Salvia miltiorrhiza,Poria cocos and Pericarpium abdominis could regulate abnormal cell apoptosis,improve antioxidant capacity and reduce lung injury by activating SIRT1,effectively prevent and treat broilers with ascites syndrome.