抑制CD36过表达减轻糖尿病大鼠心肌缺血/再灌注损伤

Inhibition of CD36 Overexpression Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

目的：探讨抑制CD36过表达在糖尿病大鼠心肌缺血/再灌注损伤中的作用和机制。方法：成年雄性健康大鼠,体重210-240g。大鼠糖尿病模型采取腹腔注射1%链脲佐菌素60mg/kg制备。大鼠冠状动脉左前降支分结扎30min后再灌注2h来制备心肌缺血/再灌注模型。正常大鼠和造模成功的糖尿病大鼠被分为3组（n=16）：非糖尿病心肌缺血/再灌注组（IR组）、糖尿病心肌缺血/再灌注组（DIR组）,CD36的抑制剂SSO处理的糖尿病心肌缺血/再灌注组（DIRS组）。再灌注结束,获取心肌组织和血样本。Western Blot法检测心肌CD36表达,TTC法检测心肌梗死面积,HE染色观察心肌组织病理变化,检测血糖,血清中胰岛素、甘油三酯（TGs）和游离脂肪酸（FFAs）。检测血清15-F2t-isoprostane、LDH、CK-MB及BNP。结果：DIR组的心肌CD36表达明显高于IR组而低于DIRS组（P〈0.05）,DIRS组的心肌缺血面积和梗死面积均减少（P〈0.05）;DIR和DIRS组糖尿病大鼠的胰岛素、TGs和FFAs的浓度均高于非糖尿病大鼠IR组（P〈0.05）,SSO处理的大鼠血清中胰岛素、TGs和FFAs的浓度均有不同程度下降（P〈0.05）。DIR组的15-F2t-isoprostane、LDH、CK-MB和BNP浓度均高于IR组（P〈0.05）,而经SSO处理后,DIRS组这些指标的浓度均有所下降（P〈0.05）。结论：SSO部分抑制CD36过表达,减轻了糖尿病大鼠心肌缺血/再灌注损伤。

Objective：To evaluate the effect and the mechanism of inhibition of CD36 overexpression on myocardial ischemia/reperfusion injury in diabetic rats.Methods：Health male adult SpragueDawley（SD）rats were adopted.Diabetes mellidus（DM）was induced by 1% Streptozotocin（STZ）intraperitoneal injection 60 mg/kg in SD rats.Non-diabetic rats and diabetic rats were randomly assigned to receive 30 min of left anterior descending artery ligation followed by 2 hof reperfusion as IR group and DIR group respectively.Sulfo-N-succinimidyloleat（SSO）is used as a specific inhibitor of CD36.The diabetic rats treated with intravenous infusion of SSO before myo-cardial ischemia were assigned as DIRS group.Sixteen rats were concluded in each group.Myocardial infarct size was determined with triphenyltetrazolium chloride staining.Myocardium was stained with HE and the pathological changes was observed under microscopy.Myocardial CD36 were determined by Western Blot.Blood glucose,insulin,TGs and FFAs were tested.Plasma15-F2 t-isoprostane,lactate dehydrogenase（LDH）release,creatine kinase-MB（CK-MB）,and plasma B-type natriuretic peptide（BNP）were measured with colorimetric assays.Results：Compared with that in DIR Group,CD36 overexpression was partially inhibited by SSO（P〈0.05）treatment,the myocardial infarct size,the content of insulin,TGs and FFAs were decreased in DIRS group（P〈0.05）,those changes were in parrallel with the level of 15-F2 t-isoprostane,LDH,CK-MB,and BNP（P〈0.05）.Conclusion：Partially inhibition of CD36 overexpression by SSO attenuated myocardial ischemia-reperfusion injury in diabetic rats.