罗格列酮对高脂血症大鼠心肌脂联素系统的调节作用

目的探讨罗格列酮对高脂血症大鼠心肌脂联素及其受体表达的影响,阐述过氧化物酶体增殖物激活受体γ(PPARγ)激动药心肌保护的新机制。方法28只WKY大鼠随机分为普通饲料组、高脂饲料组和罗格列酮(4mg·kg-1.d-1)组。24wk处死动物,采用全自动生化分析仪测定血脂,HE和Masson染色观察心肌形态学变化、测定心肌肥厚指数和平均心肌细胞直径,ELISA、RT-PCR和免疫组化法测定心肌脂联素及脂联素受体1和2(AdipoR1和AdipoR2)的表达。结果罗格列酮显著抑制高脂饮食引起的血脂升高和体重增加、抑制细胞内脂质沉积及心肌细胞肥大、增加心肌组织局部脂联素水平及其受体1基因和蛋白的表达。结论罗格列酮通过改善脂质代谢、增加心肌局部脂联素水平及其AdipoR1基因和蛋白的表达拮抗高脂血症所致心肌损害,从而发挥心肌保护作用。

Regulatory effects of rosiglitazone on cardiac adiponectin system in hyperlipidemic rats

AIM To investigate the effects of rosiglitazone on cardiac adiponectin and the expression of its receptors in hyperlipidemic rats and to clarify the cardioprotective mechanism of PPARγ agonist. METHODS Twenty-eight male Wistar-Kyoto rats were randomly divided into regular diet group, high-fat diet group and rosiglitazone group. Prior to be sacrificed at the end of 24 weeks, body weight, myocardial hypertrophy index and myocardial cell diameter were measured. Blood samples were taken by puncture of the left ventricular cavity. The concentrations of lipids in serum and the level of adiponectin in the left ventricular myocardium were measured using automatic biochemical analyzer and ELISA method, respectively. The mRNA and protein expression of adiponectin receptors (AdipoR1 and AdipoR2) in myocardium was determined using RT-PCR and immunohistochemistry. Morphology changes in myocardial tissues were observed by Hematoxylin and eosin staining ( HE) and Masson staining. RESULTS Rosiglitazone treatment significantly suppressed the characteristic pathological alterations, the increase in body weight and TC, TG and LDL-C levels induced bythe high-fat diet and suppressed the decrease in cardiac adiponectin level evoked by the high-fat diet. While rosiglitazone up-regulated the mRNA and protein expression of AdipoR1. However, the expression of AdipoR2 was not significantly different among all groups. CONCLUSION Rosiglitazone could suppress cardiac morphological abnormality caused by high-fat diet, and exert cardioprotective actions through improving lipid metabolism, increasing myocardial adiponectin level, and up-regulating mRNA and protein expression of AdipoR1 in hyperlipidemic rats.