芪蛭三七汤对心肌梗死大鼠心室重构及内质网应激凋亡的影响*

Effect of qizhi-sanqi decoction on ventricular remodeling and endoplasmic reticulum stress-related apoptosis in rats with myocardial infarction*

摘要:

目的 探讨芪蛭三七汤对心肌梗死（MI）大鼠心室重构及心肌细胞内质网应激凋亡的影响。方法 采用冠状动脉结扎法复制大鼠心肌梗死模型，分为空白对照组（n?=15）、假手术组（n?=14）、MI组（n?=11）及芪蛭三七汤干预模型组（QZ组）（n?=13）。空白对照组、假手术组和MI组大鼠均灌胃给予无菌生理盐水，QZ组大鼠灌胃给予22.68?g/kg芪蛭三七汤溶液，连续给药4周。采用超声心动图评价大鼠心功能，western blotting检测大鼠心肌细胞凋亡相关蛋白以及蛋白激酶R样内质网激酶（PERK）-真核细胞翻译起始因子2α（eIF2α）通路相关蛋白的表达。结果 ①心功能比较：与空白对照组和假手术组大鼠比较，MI组大鼠左室射血分数（LVEF）和短轴缩短率（FS）降低，而左室舒张末径（LVEDd）、左室收缩末径（LVESd）增加（P?<0.05）。QZ组大鼠LVEF和FS高于MI组大鼠，LVEDd和LVESd低于MI组大鼠（P?<0.05）。与空白对照组和假手术组大鼠比较，MI组大鼠左室压上升最大速率（+dp/dtmax）和左室压下降最大速率（-dp/dtmax）绝对值降低（P?<0.05）。QZ组大鼠+dp/dtmax和-dp/dtmax绝对值高于MI组大鼠（P?<0.05）。空白对照组和假手术组大鼠无梗死区域。QZ组大鼠梗死范围低于MI组大鼠（P?<0.05）。②心肌细胞凋亡指标：MI组大鼠非梗死区心肌凋亡指数（AI）高于空白对照组和假手术组大鼠（P?<0.05）。QZ组大鼠非梗死区心肌AI低于MI组大鼠（P?<0.05）。与空白对照组和假手术组比较，MI组大鼠心肌组织促凋亡蛋白caspase-3、Bcl-2相关X蛋白（Bax）蛋白表达量升高，而抗凋亡蛋白B淋巴细胞瘤-2基因（Bcl-2）表达量降低（P?<0.05）。与MI组大鼠比较，QZ组大鼠心肌组织Caspase-3、Bax蛋白表达量降低，Bcl-2蛋白表达量升高（P?<0.05）。③PERK-eIF2α信号通路：与空白对照组和假手术组比较，MI组大鼠心肌组织葡萄糖调节蛋白78（GRP78）、p-PERK、p-eIF2α及活化转录因子4（ATF4）蛋白表达量升高（P?<0.05）。而与MI组大鼠比较，QZ组大鼠心肌组织GRP78、p-PERK、p-eIF2α及ATF4蛋白表达量降低（P?<0.05）。结论 芪蛭三七汤可减轻大鼠心肌梗死后心室重构，其机制可能与抑制PERK-eIF2α信号通路的激活诱导的内质网应激凋亡有关。

Abstract:

Objective To discuss the effect of qizhi-sanqi (QZ) decoction on ventricular remodeling and endoplasmic reticulum stress (ERS) -related apoptosis in rats with myocardial infarction (MI). Methods Four weeks after left anterior descending coronary artery ligation, rats were administrated with QZ decoction or the same volume of saline and divided into control group (normal saline solution for 4?w, n?=?15), Sham-operation group ( normal saline solution for 4?w, n?=?14), MI model group (normal saline solution for 4?w, n?=?13) and QZ treatment group (QZ decoction for 4?w, n?=?13). Cardiac function was assessed by ultrasoundcardiogram. The cell apoptosis related proteins and PRKR-like endoplasmic reticulum kinase (PERK) - eukaryotictranslation initiation factor 2α (eIF2α) pathway related proteins were detected by Western blotting. Results ① Changes of cardiac function: rats in MI group had lower left ventricular ejection fraction (LVEF), fractional shortening (FS), +dp/dtmax, -dp/dtmax and higher left ventricular end-diastolic dimension (LVEDd), left ventricular end-systolic dimension (LVESd) than those indexes of rats in control group and sham-operation group (P??0.05). The infarction area of rats in QZ group was more than that in MI group (P?