Protective Effects and Mechanisms of Manuo Xitang GuanXinNing Extractum Against Myocardial Injury in Rats with Coronary Heart Disease
OBJECTIVE To investigate the protective effects and mechanisms of Manuo Xitang GuanXinNing extractum(GXN)against myocardial injury in rats with coronary heart disease(CHD).METHODS CHD rat model was established by high-fat diet feeding and pituitrin injection,then followed by GXN intervention.Heart rate(HR),left ventricular systolic diameter(LVIDs),left ventricular diastolic diameter(LVIDd),ejection fraction(EF)and fractional shortening(FS)of rats were measured by ultra-high resolution small animal ultrasound imaging system.Serum levels of total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lactate dehydrogenase(LDH),creatine kinase isoenzyme-MB(CK-MB)and C-reactive protein(CRP)were determined by automatic biochemical analyzer.Serum creatine kinase(CK),cardiac troponin I(cTnI),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels were determined by ELISA kits.Pathological changes of myocardial tissue of rats were observed with HE staining,and protein expressions of IL-6,IL-1β and TNF-α were detected by immunohistochemistry.Relative expressions of TLR4,PI3K,AKT and mTOR mRNA and proteins were detected respectively.RESULTS Compared with the normal group,myocardial tissue of rats in model group showed cell degeneration,necrosis and a large number of inflammatory cells infiltration.Compared with normal rats,there were significantly increased of cardiac function indicators included LVIDs and LVIDd,lipid indicators included TC,TG and LDL-C,myocardial injury indicators included LDH,CK,CK-MB,cTnI and CRP,and oxidative indicators MDA(P＜0.01).Meanwhile,the pro-inflammatory factors IL-6,IL-1β and TNF-α positively expressed in myocardial tissue.The cardiac function indexes included HR,EF and FS,oxidative indexes included SOD,GSH-Px,lipid indexes included HDL-C,as well as mRNA levels and protein expression of TLR4,PI3K,AKT and mTOR in myocardial tissue were all significantly reduced(P＜0.05).Compared with model group,GXN high-dose group could significant improvements in myocardial tissue injury,cardiac function index,lipid index,oxidative index,inflammatory factors and mRNA and protein expression of TLR4,PI3K,AKT and mTOR in myocardial tissue of CHD rats(P＜0.05).CONCLUSION GXN can improve myocardial injury and blood lipids level of CHD rats,and inhibit inflammation and oxidative stress response,which is related to the activation of TLR4/PI3K/AKT/mTOR pathway.
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