高血压大鼠血管平滑肌细胞GRP78和caspase-12表达的变化及依那普利的干预作用

Expression of GRP78 and caspase-12 in aortic vascular smooth muscle cells of hypertension rats and effects of enalapril on vascular remodeling

目的:观察高血压大鼠动脉血管平滑肌细胞(VSMCs)内质网应激(ERS)相关因子葡萄糖调节蛋白78(GRP78)和半胱氨酸门冬氨酸特异性蛋白酶12(caspase-12)表达的变化,并探讨高血压时VSMCs中ERS的分子机制,以及依那普利(enalapril,Ena)对血管重构的影响。方法:将40只健康雄性SD大鼠随机分为4组,即假手术(sham)组、sham+Ena组,腹主动脉缩窄术(AAB)组及AAB+Ena组,每组10只。4周后,通过颈动脉插管法测定大鼠血压和利用图像分析系统测量大鼠主动脉中层的厚度,并通过免疫组化染色法检测GRP78和caspase-12的表达。结果:①AAB组大鼠的平均动脉压(MAP)显著高于sham组、sham+Ena组和AAB+Ena组(P<0.05)。②AAB组大鼠血管平滑肌中层厚度显著大于sham组、sham+Ena组和AAB+Ena组(P<0.05)。③AAB组大鼠GRP78和caspase-12的表达量明显高于sham组、sham+Ena组和AAB+Ena组大鼠。结论:AAB所致的高血压可触发动脉血管平滑肌细胞过长过强的ERS。Ena可能通过下调ERS的水平,逆转高血压所致VSMCs损伤的作用,对VSMCs具有保护作用。其作用机制可能与其降低caspase-12介导的ERS反应有关。

AIM： To examine the effect of endoplasmic reticulum stress （ERS） on vascular remodeling induced by hypertension and to observe the effects of enalapril on the expressions of the correlation factors GRP78 and caspase-12 in vascular smooth muscle cells （VSMCs） and their relationship with vascular changes. METHODS： Forty adult male SD rats were randomly divided into sham operation group, sham ＋ Ena group, AAB group and the AAB ＋ Ena group. Four weeks later, MBP was measured through carotid artery incubation, the aortic media thickness was measured by image analyses software and the expressions of GRP78 and caspase-12 in the vascular smooth muscle cells were examined by immunohisto- chemistry. RESULTS ： MAP of AAB group rats was significantly higher than those of rats in sham opera- tion group, sham ＋ Ena group and AAB ＋ Ena group （P 〈 0. 05 ）. The aortic media thickness of AAB group rats was significantly thicker than those of rats in sham operation group, sham ＋ Ena group and the AAB ＋ EJaa group （P 〈 0. 05）. The expressions of GRF78 and caspase-12 of AAB group rats were significantly higher than those of rats in sham group, sham ＋ Ena group and AAB ＋ Ena group. CONCLUSION： High blood pressure resulting from abdominal aortic bounding causes endoplasmic reticulum stress response of vascular smooth muscle cells. Enalapril may exert some protective effects on VSMCs by inhibiting the endoplasmic reticulum stress via downregulation of the expression of caspase-12.