目的研究决明子提取物(SCE)对糖尿病大鼠心肌缺血/再灌注(MI/R)损伤的影响。方法构建高脂饲料-链脲霉素诱导的2型糖尿病大鼠模型(HFD-STZ),大鼠随机分为对照组(Con)、SCE处理组(Con+SCE,每日灌胃给予SCE,10 mg/kg)、糖尿病组(DM)和糖尿病SCE处理组(DM+SCE)。1周后行心肌缺血30 min/再灌注4或6 h,并检测血浆总胆固醇(TC)和三酰甘油(TG)水平,用伊文氏蓝-TTC法检测心肌梗死范围、用试剂盒检测血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性、用TUNEL法和caspase-3试剂盒检测细胞凋亡,用Western blot法检测Akt、ERK1/2表达及磷酸化等。结果 HFD-STZ大鼠MI/R损伤加重,虽SCE处理1周对正常动物MI/R损伤无影响,但降低HFD-STZ大鼠TC、TG水平,可将其心肌梗死面积减小至38.4%±2.7%,显著低于糖尿病组的46.1%±3.2%(P<0.05),且血清CK、LDH活性及细胞凋亡减少;还可增加HFD-STZ大鼠心肌Akt及ERK1/2磷酸化。用Akt或ERK1/2抑制剂可阻断SCE的心肌保护作用。结论 SCE可有效减轻糖尿病大鼠MI/R损伤,可能与其降脂并激活Akt及ERK1/2信号有关。
Objective Obese patients with type 2 diabetes mellitus ( T2DM) characterized by hyperglycemia are li-able to more severe myocardial infarction .Semen Cassiae is proved to reduce serum lipid level .This study was to investigate whether the Semen Cassiae extract (SCE) reduces myocardial ischemia and reperfusion (MI/R) injury with or without diabetes and the underlying mechanisms .Methods The high-fat diet-fed streptozotocin ( HFD-STZ) rat model was used as T2DM model.Normal and DM rats received SCE treatment orally (10 mg/kg/day) for 1 week.Subsequently these animals were subjected to MI /R.Results Compared with the normal animals , DM rats showed increased plasma total cholesterol ( TC) and triacylglycerol ( TG) , more severe MI/R injury and cardi-ac functional impairment .SCE treatment significantly reduced the plasma TC and TG , improved the instantaneous first derivation of left ventricle pressure and reduced infarct size , decreased plasma creatine kinase and lactate dehydrogenase levels, and reduced apoptosis index at the end of reperfusion in diabetic rats .Moreover, SCE treat-ment increased the antiapoptotic protein Akt and stimulated ERK 1/2 phosphorylation .Pretreatment with a PI3 K in-hibitor wortmannin or an ERK1/2 inhibitor PD98059 not only blocked Akt and ERK1/2 phosphorylation, but also inhibited the cardioprotective effects of SCE .However , SCE treatment did not show any effects on the MI/R injury in the normal rats.Conclusions SCE effectively improves myocardial function and reduces MI/R-induced injury in diabetic but not normal animals , which is potentially attributable to the reduced TC/TG levels and the triggered cell survival signaling Akt and ERK 1/2 .