The Effects On Myocardial Fibrosis And Cardiac Function Of Diabetic Rats By Using Hedysarum Polybotys Saccharide Alone Or Combining With Irbesartan

Objective To study the effects on myocardial fibrosis and cardiac function of diabetic rats by using Hedysarum polybotys saccharide alone or combining with lrbesartan and its potential mechanism,supply the theoretic and experimental evidence for preventing the development of diabetic myocardial fibrosis.Methods50male Wistar rats were randomly divided into two groups:normal control group(NC group) and modeling group. NC group was fed with the normal diet. The remaining rats were used to establish diabetic animal models by feeding high glucose and fat diet and intraperitoneal injecting low-dose streptozotocin. After the success of modeling,37diabetic animal models were randomly divided into four groups, namely diabetes mellitus group(DM group,n=10), Hedysarum polybotys saccharide intervention group (HPS group,n=9).Irbesartan intervention group(IRB group,n=9) and Hedysarum polybotys saccharide combined with Irbesartan intervention group(combined group,n=9). HPS group and IRB group were respectively intervened by intragastric administration with Hedysarum polybotys saccharide (150mg/kg) and Irbesartan (30mg/kg) every day;combined group were intervened by intragastric administration with Hedysarum polybotys saccharide (150mg/kg) plus Irbesartan (30mg/kg) every day;NC group and DM group were given normal saline once a day. After8weeks intervention, all rats were anesthetized by10%chloral hydrate before we took the myocardial samples. The heart weight was tested and calculate heart weight/body weitht(H/B).The levels of serum brain natriuretic peptide was tested by ELISA.Content of the left cardiac ventricle myocardial collagen was observed by Masson Staining test.The expression levels of cardiac transforming growth factor beta1(TGF-β1), Smad3and Smad7protein were detectd by immunohistochemical method.The expression levels of TGF-β1, Smad3and Smad7mRNA were detected by real-time quantitative PCR. Myocardial ultrastructure was observed by the electron microscopy.Results1. Myocardial ultrastructure and masson staining results:Myocardial fibrosis of DM group was obvious.collagen content was higher than NC group, HPS group, IRB group and combined group. Compared with DM group, myocardial fibrosis in HPS group, IRB group and combined group were attenuated,collagen content reduced,the differences between them was statistically significant.Compared with HPS group and IRB group, the myocardial fibrosis was reduced in combined group, the differences between them was statistically significant.2.The expression of myocardial TGF-β1, Smad3, Smad7:The expression of TGF-β1,Smad3in DM group were higher than other groups while the expression of Smad7was reduced.The levels of TGF-β1and Smad3in HPS group,IRB group and combined group were higher than NC group,but less than DM group.The expression of Smad7in HPS group,IRB group and combined group were less than NC group,but higher than DM group. And the change of expression of TGF-β1, Smad3, Smad7in combined group were obvious than HPS group and IRB group,the differences between them was statistically significant.3. Comparison of serum BNP:The levels of serum BNP in DM group was higher than other groups. While the levels of BNP in HPS group,IRB group and combined group were lower than DM group but higher than NC group,and the levels of BNP in combined group was lower than HPS group and IRB group,the differences was statistically significant.Conclusion1. Myocardial fibrosis in diabetic rats could be reduced and the cardiac funtion was improved by using Hedysarum polybotys saccharide and Irbesartan,the effects of them in combination is better than that used alone.2.The potential mechanism of Hedysarum polybotys saccharide and Irbesartan on myocardial fibrosis of diabetic rats may be related to TGF-β1/Smads signal transduction pathway.