中文摘要：

探讨抗细胞凋亡在联合应用吗啡和肢体远隔缺血后处理（remote ischemic postconditioning, RIP）心肌保护中的作用。 方法 采用大鼠在体心肌缺血/再灌注损伤（ischemia/reperfusion injury, I/RI）模型，根据随机数字表法将60只SD大鼠分为4组（每组15只）：缺血/再灌注（ischemia/reperfusion, I/R）组（I/R组）、肢体RIP组（RIP组）、吗啡后处理组（M组）以及联合应用吗啡和肢体RIP组（M＋RIP组）。再灌注末留取缺血中心区、缺血边缘区和非缺血区心肌组织标本，应用Tunel染色法检测心肌细胞凋亡指数（apoptotic index, AI），应用实时定量PCR技术检测心肌细胞凋亡相关基因Bcl-2 mRNA和Bax mRNA表达，光学和电子显微镜观察缺血中心区心肌细胞形态。 结果 I/R组、RIP组、M组和M＋RIP组缺血中心区心肌细胞AI分别为（49.1±4.9）%、（34.2±2.9）%、（39.7±3.2）%和（29.0±4.9）%，缺血边缘区心肌细胞AI分别为（12.7±2.2）%、（8.2±1.6）%、（10.4±2.7）%和（5.9±1.4）%。在缺血中心区和缺血边缘区，M＋RIP组心肌细胞AI较I/R组和M组明显降低（P＜0.05），M＋RIP组的Bcl-2 mRNA表达较I/R组、RIP组和M组明显增强（P＜0.05），而M＋RIP组的Bax mRNA表达则较I/R组、RIP组和M组明显降低（P＜0.05），M＋RIP组的Bcl-2/Bax较I/R组、RIP组和M组明显升高（P＜0.05）。光学和电子显微镜检查显示，M＋RIP组的心肌形态和线粒体结构明显改善。 结论 Bcl-2相关信号通路的细胞凋亡抑制是联合应用吗啡和肢体RIP的心肌保护作用机制之一。

英文摘要：

Objective To evaluate the role of anti-apoptosis in protection of combined morphine and limb remote ischemic postconditioning（RIP） against myocardial ischemia/reperfusion injury（I/RI）. Methods Sixty male SD rats were randomly allocated into four groups（n=15）： ischemia/reperfusion（I/R） group（group I/R）, group RIP, morphine group （group M）, and combined morphine and RIP group（group M＋RIP） . The apoptosis in the myocardial ischemic core, ischemic border and non-ischemic areas were assessed through the Tunel assay and real-time PCR for Bax mRNA and Bcl-2 mRNA. Optical and electronic microscopes were used to determine the cardiomyocyte morphology. Results The apoptotic index（AI） of myocytes in the ischemic core area was （49.1±4.9）%, （34.2±2.9）%, （39.7±3.2）% and （29.0±4.9）% in the I/R, RIP, M, M＋RIP groups, respectively. The AI of myocytes in the ischemic border area was（12.7±2.2）%, （8.2±1.6）%, （10.4±2.7）% and （5.9±1.4）% in the I/R, RIP, M, M＋RIP groups, respectively. In the ischemic core and border area, the AI of myocytes was significantly decreased in the M＋RIP group compared to that in the I/R and M groups（P〈0.05）, the expression of Bcl-2 mRNA was significantly increased（P〈0.05） and expression of Bax mRNA was significantly decreased in group M＋RIP（P〈0.05）, compared to that in the I/R, RIP, and M groups. Bcl-2/Bax ratio was significantly increased in group M＋RIP（P〈0.05）, compared to that in the I/R, RIP, and M groups. Optical and electronic microscopes showed that myocardial morphology and mitochondrial structures were significantly improved in group M＋RIP. Conclusions Apoptotic inhibition by Bcl-2 linked signaling pathway is one of the mechanisms of cardioprotection by combining morphine and limb RIP against I/RI.