过氧化物酶体激活物受体和脂肪酸代谢在糖尿病性心肌病中的作用

The alterations of peroxisome proliferator-activated receptor alpha(PPARα) and free fatty acids in STZinduced diabetic cardiomyopathy rats.

目的研究过氧化物酶体激活物受体α(PPARα)及游离脂肪酸(FFA)在糖尿病心肌病(DCM)中的作用。方法雌性Wistar大鼠,随机选出对照组给予普通饮食;其余饲以高脂高糖饮食4周后,小剂量链脲佐菌素(STZ)诱导2型糖尿病,经16周饲养诱导心肌病发生(DCM组),超声评价心功能、病理以及超微病理改变,检测生化指标、心肌胶原和PPARα的表达。结果与对照组相比,DCM组心功能减退,心脏重量指数、胶原分数增加,Ⅰ、Ⅲ型胶原的比值显著增加(P<0.01);心肌超微结构显示肌纤维变性坏死,间质胶原增多,微血管基底膜改变等;血糖、胰岛素胆固醇、甘油三酯升高,FFA增加,PPARα的表达显著增加。结论糖尿病心肌中PPARα-FFA能量代谢信号通路的变化可能与心室重塑有密切关系,是心肌病发病的重要原因。

Objective To investigate the effect of PPARα and Free Fatty Acids （FFA） in the development of diabetic cardiomyopathy. Methods Rats were randomized into control group feeding with general diet and experimental group, which were fed with high glucose and hyperlipid diet for 4 weeks. Then diabetes mellitus was induced by a single injection of STZ. After another 16 weeks feeding, Hemodynamic characterization, the myocardial pathologic and ultrastructure changes was observed. The collagen volume fraction and the expression of type Ⅰ, Ⅲ collagen and PPARα were quantified by digital image analysis, and plasma biochemical indicators were detected also. Results Compared with the control group, the diastolic function deteriorated in DCM-group followed with higher Hw/Bw ratio, CVF, Col ⅠCol Ⅲratio. The ultrastructure of DCM heart presented focal degeneration and disarranged order of myofilament, increased interstitial collagen and glycogen granule deposited, etc. There were elevated plasma concentrations of glucose, insulin, cholesterol, TG and FFA in DCM group, paralleled by abundant PPARα expression. Conclusion The expression alterations of PPARα and metabolism changes of FFA involve in the abnormality of myocardial metabolism and myocardial remodeling, and possibly play an important role in the development of diabetic cardiomyopathy.