雷米普利对实验性心力衰竭大鼠心肌细胞凋亡和Fas Fas配体基因表达的影响

Effects of ramipril on expression of Fas/FasL genes in experimental hypertensive Wistar rats

目的探讨实验性心力衰竭大鼠心肌细胞凋亡和心肌组织Fas、Fas配体(FasL)蛋白及信使核糖核酸(mRNA)表达的变化及血管紧张素转换酶抑制剂(ACEI)干预的影响及意义。方法将30只健康Wistar大鼠,随机分为假手术组、慢性心力衰竭组和雷米普利组各10只。通过缩窄Wistar大鼠腹主动脉建立慢性心力衰竭模型,以雷米普利进行干预,对照观察血流动力学、心肌细胞凋亡、心肌组织Fas、FasL蛋白及其mRNA表达的变化。结果与假手术组相比,慢性心力衰竭组左心室舒张末压、心率显著升高(P<0.01);收缩压、舒张压、平均动脉压、左心室收缩压、左心室内压最大收缩率、左心室内压最大舒张率显著降低(P<0.01)。雷米普利组舒张压、左心室收缩压、左心室舒张末压、心率显著低于慢性心力衰竭组(P<0.01),左心室内最大收缩率、左心室内最大舒张率显著高于慢性心力衰竭组(P<0.01)。慢性心力衰竭组心肌细胞凋亡指数、心肌组织Fas、FasL蛋白及其mRNA表达水平显著低于慢性心力衰竭组(P<0.05)。结论慢性心力衰竭的发生、发展过程中有心肌细胞凋亡的变化及Fas/FasL系统的参与;心力衰竭大鼠心肌细胞凋亡指数、心肌组织Fas、FasL蛋白及其mRNA表达水平增高,雷米普利长期干预慢性心力衰竭,能够降低细胞凋亡及Fas、FasL基因的表达,可能与其减少Fas/FasL系统介导的细胞凋亡的发生、改善心功能有关。

Objective To study the effects of ramipril on myocyte apotosis and expression of Fas and FasL genes of cardiomyocytes in experimental hypertensive rats, Methods After the model with chronic heart failure was established by gradually constricting the abdominal aorta of Wistar rats, the animals were divided into heart failure group and ramipril treated group. Other 10 sham-operated rats were as control group. Hemodynamic parameters were determined. Terminal deoxynucleotidyl transferase-mediated dUTE nick end labeling （TUNEL） and ABC staining were used respectively to detect the changes of apoptosis and protein expression of Fas and FasL genes,and mRNA expression of Fas gene was evaluated by RT-PCR analysis. Results Compared with control group, left ventricular end-diastolic pressure （LVEDP） in heart failure group was（ P 〈 0.01 ）, while ＋ dp/dtmax and - dp/dtmax were significantly decreased （P〈0.01）. LVEDP was lower but ＋ dp/dtmax and -dp/dtmax were significantly higher in ramipril treated group （P〈0.01）. When the heart failure occurred, apoptosis index （AI） and positive index （PI） of Fas and FasL protein in myocytes were increased more significantly （P〈0.05） than those in shame group. The apoptosis index （AI） and the expression of Fas and FasL genes in ramipril group were significantly lower than those in heart failure group （P 〈 0.05）. Conclusion The mentioned parameters suggest that Fas/FasL system is involved in the occurrence and development of chronic heart failure. Ramipril administration for a long time in case of chronic heart failure may decrease the expression of Fas and FasL genes. This can be associated with the reduction of myocyte apoptosis and the improvement of myocardial function.