The Effects Of Yiqihuoxue On Myocardial Ischemia And The Expression Of Intercalated Disk Related Protein Of Rats

Objective:The myocardial ischemic rats subjected with coronary artery ligation were adopted to screen the best composition of Yiqihuoxue preparation. The optimistic Yiqihuoxue was adimistered to above-mentioned experimental rats, its protective effects on myocardial ischemic injury and possible mechanism was attempted to probe.Methods:Part Ⅰ:Prescription optimzing:Healthy rats were randomly divided into eight groups, low and high-dose group of YiQiHuoXue (YQHX) prescription1,2,3, Diltiazem and vehicle group, and were treated with tested article for seven times. After that, the left anterior descending coronary of rats was ligated to develope myocardial ischaemia rat model.4h later the rats were decapitated, their hearts were removed to slice and were stained with1%TTC to distinguish the infarction area with non-infarction area. The myocardial infarction size ratio was caculated with the formula, ratio=(infarction area weight/whole heart weight)×100%.Part Ⅱ:the protective effects of YiQiHuoXue on myocardial ischemic ratsRats were randomly divided into6groups, YQHX low, medium and high-dose group, vehicle group, sham group and Diltiazem group, and given treatentment for seven times. The acute myocardial infarction model was developed with coronary artery ligation. After4h for the surgery, peak left ventricular pressure (LVP) and other cardiac function were detected through right common carotid artery cannulation to the left ventricular. The hearts were removed and fixed to observe morphological changes with light microscopy and electron microscopy. The blood sample was collected from carotid to test the content of cTnT, cTnI following the kit instruction.Part III:the mechanism of YQHX antagonizing myocardial ischemiaRats were randomly divided into six groups:sham group, vehicle group, Diltiazem group, YQHX low, medium, high dose group, and administered with tested article for seven times. After that the acute myocardial infarction rats were developed with coronary artery ligation.4h later the blood sapmple was collected from carotid to measure SOD, MDA, GSH in serum following the kit instruction. The hearts were fixed to observe the expression of N-cadherin, desmoplakin, connexin43with the methods of immunohistochemistry(IHC), western-blot and RT-PCR.Results:Part I:Compared with the vehicle group, YQHX1and YQHX2could reduce the size of the myocardial infarct. The Diltiazem group reduced myocardial infarction size by42.4%, YQHX1low and high-dose group dcreased myocardial infarction size about24.5%、31.8%, high-dose group of YQHX2reduced myocardial infarction size obviously, by54.8%.Part II:The results showed that, compared with vehicle group, Diltiazem group inhibited myocardial infarction size by44.4%, YQHX low, medium and high dose group both reduced the size of the myocardial infarct obviously(P<0.05,P<0.01). Compared with the vehicle group, the medium and high-dose YQHX could obviously increased the LVP (P<0.05), high-dose YQHX could obviously increase the+LVdp/dtmax and-LVdp/dtmax (P<0.05), it indicated that YQHX could improve the cardiac function of the myocardial ischemic rats.Under Light microscopy analysis, bleeding, gathered inflammatory cells, myocardial cells death and structure chaos were found in myocardial infarction area of vehicle rats. And medium and high-dose YQHX could decrease myocardial cells death. Under electronic microscopy, partial cytoplasm of fibroblast enlarged slightly, some fraction of collegen fibrosis and capillary vessel were found on the side of rough endoplasmic reticulum in heart tissue of vehicle rats,.while the ultrastructure damage of YQHX group rats was recovered remakedly. After the surgery of ligating coronary artery, the content of cTnT、cTnI was raised obviously in the serum of vehicle group rats(P<0.05,P<0.01), and YQHX could reduce the content of cTnT significantly (P<0.05).Part Ⅲ:The result showed that, compared with the vehicle group, high-dose of YQHX could significantly increase the activity of GSH and SOD in the serum(P<0.05), the medium and high-dose YQHX could obviously reduce the content of MDA (P<0.05). The results suggested that YQHX has antioxidant effects to some extent. The expression of N-cadherin, desmoplakin, connexin43increased significantly in myocardial tissue of midium and high-dose YQHX rats with the increase of the dosage of YQHX. Through IHC and westernblot analysis, the expression of Cx43, N-cadherin was raised with the increase of YQHX dosage.Conclusion:The YiQiHuoXue could reduce the myocardial infarction size, improve cardiac function of myocardial ischaemic rats significantly. The mechanism may be related with increasing the expression of N-cadherin, desmoplakin, connexin43of myocardial intercalated disk to improve the information transfer between myocardial cells, and resisting free radical injury.