内质网应激对心肌梗死后心力衰竭大鼠心肌组织的作用

目的 研究内质网应激对心肌梗死后心力衰竭大鼠心肌组织的作用。方法 结扎大鼠左冠状动脉前降支建立心肌梗死后心力衰竭(心衰)模型，大鼠随机分为：假手术组、手术组术后2周组、4周组、6周组和8周组，测量各组大鼠的血流动力学指标，用荧光定量PCR方法检测各组大鼠的内质网分子伴侣GRP78蛋白，内质网应激相关凋亡蛋白CHOP、Caspase-12、Caspase-3、Bcl-2在心肌组织中的表达量。结果 与假手术组相比较，手术组大鼠左室收缩压(LVSP)、左室压最大上升和下降速率(±dp/dt max)明显低于假手术组(P≤0.05 或 P≤0.01)；左室舒张末压(LVEDP)则高于假手术组(P≤0.05)。手术组大鼠心肌组织中GRP78、CHOP、Caspase-12、Caspase-3的表达量随术后饲养时间的增长而增高(P<0.05或P≤0.01)，且表达量与术后饲养时间呈正相关(P≤0.01)；心肌组织中Bcl-2的表达量随术后饲养时间的增长逐渐降低(P≤0.01)，表达量与术后饲养时间呈负相关(P≤0.01)。结论 内质网应激激活了相关的细胞凋亡通路，使得心肌细胞凋亡。

Effect of Endoplasmic Reticulum Stress in Rat Congestive Heart Failure Induced by Myocardial Infraction

Objective To explore the effect of endoplasmic reticulum stress in rat congestive heart failure induced by myocardial infraction. Method The rat model of heart failure was established by ligating the left anterior descending coronary to produce acute myocardial infarction．The rats were divided into 5 groups：sham group and groups of post-operation at time points of 2, 4, 6 or 8 weeks, respectively. The ventricular functions were assessed by hemodynamic.The expression of GRP78, CHOP, caspase-12, caspase-3,and Bcl-2 were detected by Q-PCR. Result Left ventricular systolic pressure (LVSP) and maximal rise and decline velocity of left ventricular pressure decreased (P≤0.05 or P≤0.01), but left ventricular end diastolic pressure (LVEDP) increased (P≤0.05) in model group compared with sham group. The expression of endoplasmic reticulum chaperones GRP78, CHOP, caspase-12 and caspase-3 was significantly increased (P≤0.05 or P≤0.01) in model group compared with sham group. And the expression were positively correlated (P≤ 0.01)with the feeding time of post-operation. The expression of Bcl-2 was reduced gradually (P≤0.01) in model group compared with sham group;And the expression were negatively correlated (P≤0.01)with the feeding time of post-operation. Conclusion The congestive heart failure induced by myocardial infraction is associated with endoplasmic reticulum stress. It suggest that endoplasmic reticulum stress-induced apoptosis is a possible mechanism of heart failure effecting on promoting.