妊娠期糖尿病对大鼠雌性子代缺血再灌注后心脏收缩功能的影响及其机制

Effects of gestational diabetes mellitus on cardiac contractile function of female offspring rats after ischemia / reperfusion and underlying mechanisms

目的利用大鼠模型探讨妊娠期糖尿病(GDM)对雌性子代心脏功能的影响及潜在机制。方法雌性野生型SD大鼠在妊娠中期给予腹腔注射链脲佐菌素(35 mg/kg)建立GDM模型(GDM组),另设正常对照组。分娩后,雌性F1子代饲养至24周,期间测定随机血糖、血压和心率,进行葡萄糖耐量试验、胰岛素耐量试验。构建心脏离体缺血再灌注(I/R)模型,Western blotting检测心脏蛋白激酶B(Akt)、腺苷酸激活蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)信号通路。结果 GDM组雌性F1子代离体I/R后心脏收缩功能显著低于正常对照组(P=0.048 6);Western blotting显示离体I/R后GDM组雌性F1子代大鼠心脏AMPK和ACC磷酸化水平显著低于正常对照组(P=0.005 6)。结论 GDM可引起子代雌性大鼠对心脏I/R损伤不耐受,这可能与其心脏AMPK磷酸化对I/R刺激反应迟钝有关。

Objective To investigate the effects of gestational diabetes mellitus（GDM） on the cardiac function of female offspring rats and underlying mechanisms by the rat model.Methods Wild type female SD rats were injected with streptozotocin（35 mg/kg） in the second trimester of pregnancy to establish the GDM model（GDM group）.The control group was also established.Female F1 offspring rats were fed for 24 weeks after they were born.During this period,random blood glucose level,blood pressure,and heart rate were measured and glucose tolerance test and insulin tolerance test were conducted.The invitro myocardial ischemia/reperfusion（I/R） model was established.The signaling pathways of protein kinase B（Akt）,adenine monophosphate activated protein kinase（AMPK）,and acetyl-coenzyme A carboxylase（ACC） in cardiac tissues were detected by Western blotting.Results The in vitro cardiac contractile function of female Fl offspring of the GDM group after I/R was significantly weaker than that of the control group（P = 0.048 6）.The results of Western blotting showed that the phosphorylation of AMPK and AC C in cardiac tissues of female Fl offspring of the GDM group after invitro I/R was significantly lower than that of the control group（P = 0.005 6）.Conclusion GDM results in cardiac I/R intolerance of female offspring rats,which may be relevant to the blunt response to I/R stimulation caused by the phosphorylation of AMPK.