摘要
目的探讨过氧化物酶体增殖物激活型受体α(PPARα)配体非诺贝特对压力超负荷致大鼠左心室肥厚过程中动态心肌细胞凋亡的影响。方法雄性Wistar大鼠腹主动脉缩窄致压力超负荷模型,术后48h存活的40只随机分成(1)手术组(CAA组),假手术组(SH组),(2)非诺贝特组(F组)30mg/kg.d,每组又按术后4周、8周两个时相,随机分为4周和8周组2个亚组,每组10只;(3)另取10只Wistar雄性大鼠,只穿线不节扎以作对照。给药干预4周、8周后检测血流动力学参数、心室重塑指标;采用脱氧核苷酸末端转移酶介导的缺口末端原位标记(TUNEL)法,检测心肌细胞凋亡指数(CAI);用West-ern-blot法观察PPARα蛋白的表达变化。结果与假手术组相比,非诺贝特处理4周时对血流动力学、心肌重塑指标及心肌细胞凋亡无明显影响,但8周时显著上调了PPARα蛋白表达,减轻了压力超负荷诱导的心肌肥厚,改善了血流动力学指标,抑制了心肌肥厚过程中的心肌细胞凋亡。结论PPARα配体长期(8周)能减轻压力超负荷大鼠的心肌肥厚,抑制心肌细胞凋亡,对心力衰竭进程中的心肌重塑有改善作用。
Objective To investigate the effects of ligands of PPARα on rat cardiac apoptosis in pressure-overloaded leh ventricular hypertrophy. Methods A pressure overloading model was established by the banding abdominal aorta in Wistar rats. Forty-eight hours after the procedure, the 40 surviving rats were randomly divided into two groups： （1）Coarctation of abdominal aorta（CAA） and controls, sham-operated（SH）group. （2） fenofibrate（30 mg/kg·d） group by gastric garage. After 8 weeks of therapy, hemodynamic studies were performed, LVW/BW ratio and the RVW/BW ratio were determinated DNA fragmentations were determined semiquantitatively by TUNEL and the PPARα expression by Western blot. Results Left ventricular hypertrophy and hemodynamic parameters was ameliorated by PPARα ligands （fenofibrate） treatment 8 weeks but little effect was found at 4 weeks. Fenofibrate significantly （P〈0. 05） increased the level of protein expression of PPARa while reduced cardiocyte apoptosis in pressure-overload rats. Conclusion These data suggest that chronic treatment （8 weeks） with the PPARα agonist activated PPARα expression and may be useful in preventing cardiac hypertrophy and apoptosis.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2006年第9期719-723,共5页
Chinese Journal of Hypertension
基金
贵州省科技攻关项目(黔科合2004NGY043)
