To Observe The Regulatory Role Of Leptin Pretreatment On Type2Diabetic Rats With Myocardial Ischemic Reperfusion Injury

Objective:(1) To investigate the effects of leptin pretreatment on myocardialischemic reperfusion injury (MIRI) in diabetic rats, and to explain themechanism of protective effects.(2) To establish the diabetic cardiomyopathy ratmodel, then observe the effects of leptin on ventricular remodeling in diabeticcardiomyopathy rats. Methods:(1) Sevetny healthy SD rats were randomlydivided: normal control group (n=10) and diabetes mellitus group (DM, n=60),the NC group fed on basic diet for4weeks and high fat/high sucrose diet. TheDM rats were randomly divided into five froups with10in each group: DMsham operation group, DM-MIRI group, low-dose-leptin group,middle-dose-leptin group, high-dose-leptin group. The blood and heart sampleswere obtained from each rat after reperfusion. The levels of serum tumornecrosisfactor-alpha(TNF-а), malondialdehyde(MDA), superoxidedismutase(SOD), fasting blood glucose(FBG), leptin and homeostasis modelassessment-IR (HOMA-IR), were detected.(2) Ten healthy male SD rats (SPF,8weeks,weighing170~190g) were selected as normal control group (NC),those who were given normal diet. Then other fifty healthy SD rats (SPF,8weeks,weighing170~190g) were intraperitoneally injected twice withstreptozocin (STZ) to induce diabetic cardiomyopathy. The diabeticcardiomyopathy rats were randomly divided into three groups: the DCM group （n=10）, the50μg/kg leptin group (n=10) and the100μg/kg leptin group(n=10). The diabetic cardiomyopathy rats were fed on high fat/high sucrose diet.In the eleventh weeks, the latter two groups were respectively given dailyintraperioneal injections of leptin on50μg/kg and100μg/kg, while the NC andA groups were injected with distilled water for5days. The levels of FBG, FINS,Leptin, Ang-Ⅱ, left ventricular weight index, LVEDP, LVIDd, and LVEF wereanalyzed after12weeks later. Results:(1) Compared with normal control group,the levels of FBG、FINS、TNF-а, MDA, leptin, HOMA-IR, TG, TC and LDL-Cof diabetic rats were increased, the levels of SOD and HLD-C were decreased(P＜0.05); Compared with DM sham operation group, the levels of FBG, FINS,leptin and HOMA-IR of rats in DM-MIRI group, low-dose-leptin group,middle-dose-leptin group, high-dose-leptin group were significantly increased,the levels of TNF-аand MDA of rats in DM-MIRI group were increased, thelevels of SOD were decreased, the levels of TNF-а, TG, TC, LDL-C andHDL-C of rats in low-dose-leptin group, middle-dose-leptin group,high-dose-leptin group were increased, and the levels of SOD were decreased(P＜0.05); Compared with DM-MIRI group, the levels of FBG、FINS、TNF-α, MDA, leptin, HOMA-IR,TG, TC and LDL-C of rats in low-dose-leptingroup and middle-dose-leptin group group were significantly decreased, thelevels of SOD and HDL-C were increased (P＜0.05). HE staining resultsshowed that the myocardial tissue of rats in DM-MIRI model group had seriousinjuries, the diabetic rat myocardial cells were hypertrophy and deformation.The myocardial tissue was partly necrosis and hemorrhage, and the myocardialfibers were derangement, and the myocardial cells were visible and arrangedloosely and disorderly with infiltration of inflammatory cells of rats inmesenchyme; the myocardial cells in middle-dose-leptin group were still hypertrophy and deformation, and the myocardial structure was disorder,however the hemorrhage, necrosis, and neutrophils aggregation of myocardialtissue were significantly reduced, and lesions improved significantly; while thepathological changes of rats in low-dose-leptin group were less than themiddle-dose-leptin group；the high-dose-leptin weren’t changed significantly.(2)There were abnormal cardiac function in DCM rats. The left ventricular weightindex, leptin, FINS and Ang-Ⅱin DCM groups was significantly higher thanthat of the controls (P＜0.05). After the intervention of leptin, the cardiacfunction decline was more severe while the left ventricular weight index, leptin,FINS and Ang-Ⅱwere higher than that of group A (P＜0.05)， and especiallyfor rats in group C. Conclusion:(1) Metabolic disorders of insulin resistanceand leptin resistance are observed in type2diabetic rats with myocardialischemic reperfusion injury. Certain concentration leptin pretreatment showsprotective effects on type2diabetic rats with myocardial ischemic reperfusioninjury, which can reduce the levels of leptin, TNF-α, MDA and HOMA-IRlevels, and increase SOD levels, thus may reduce the injury by inflammation,oxidative stress, dyslipidemia and insulin resistance to protect the myocardialtissue and to alleviate the MIRI in diabetic rats.(2) Leptin may be involved inoccurrence and development of diabetic cardiomyopathy, leptin can activates therennin angiotensin system and inflammatory factors which may be one of thepathologiesis of diabetic cardiomyopathy．.