HIF-1α稳定表达抑制缺血再灌注大鼠心肌细胞凋亡的作用研究  

Anti-apoptotic effect of HIF-1α stable expression on myocardial ischemia-reperfusion in rats

作　　者：刘艳[1] 李玲萍[1] 张红霞[1] 张炜芳[1] 王丽月[1] 薛晋红[1] 贺忠梅[1] 

机构地区：[1]山西医科大学基础医学院生理学系,细胞生理学山西省重点实验室,山西省太原市030001

出　　处：《中国心血管病研究》2016年第3期277-280,286,287,共6页Chinese Journal of Cardiovascular Research

基　　金：山西省自然科学基金（项目编号：2012011040-7）;医学电生理四川省重点实验室开放基金（项目编号：2011-2）;山西医科大学博士启动基金（项目编号：03201106）

摘　　要：目的探讨低氧诱导因子-1α（HIF-1α）稳定表达对大鼠心肌缺血再灌注细胞凋亡的影响及可能机制。方法采用结扎冠脉左前降支45min，再灌注3h的方法，构建大鼠心肌缺血再灌注损伤模型。实验分为假手术组（Sham）、心肌缺血／再灌注组（MI／R）、HIF-1α活化剂DMOG＋心肌缺血／再灌注组（D＋MI／R）、HIF-1α抑制剂YC-1＋心肌缺血，再灌注组（YC-1＋MI／R），采用全自动生化分析仪测定血清心肌酶（CK—MB，LDH）活性，Western blot检测心脏组织HIF-1α蛋白表达，Evens blue／Trc染色测定心肌梗死面积，TUNEL染色及Caspase-3、8、9活性测定心肌细胞凋亡。结果①与MI／R组相比，D＋MI／R组的HIF-1α蛋白表达量增加约4．6倍（P〈0．01），心肌酶CK—MB、LDH的活性降低（P〈0．05），心肌梗死面积减小（P〈0．05），并且心肌组织的病理损伤减轻。②D＋MI／R组心肌细胞凋亡率为（9．7±0．98）％，明显低于MI／R组的（23．5±1．5）％（P〈0．05），且部分逆转了缺血再灌注后心肌组织Caspase-9和Caspase-3的活性升高（P〈0．05）。结论HIF-1α稳定表达可抑制线粒体途径介导的心肌细胞凋亡，从而发挥对缺血再灌注损伤的心脏保护效应。Objective To investigate the effect of HIF-1α stable expression on myocardial apoptosis in ischemia-reperfusion rats. Methods The rat model of MI/R injury was induced by 45 min of transient vessel occlusion followed by 3 h of reperfusion. Rats were randomised into four equal groups： pseudo surgery group （Sham group）, myocardial ischemia/reperfusion group （MI/R group）, HIF-1α activator DMOG＋myocardial ischemia/ reperfusion group（D＋MI/R group） and HIF-1α inhibitor YC-1＋myocardial ischemia/reperfusion group（YC-1＋MI/ R group）, at the end of the experiment, blood samples were taken for the measurement of serum levels of CK-MB and LDH by fully automatic biochemical analyser, the protein levels of HIF-1α were detected via Western blot analyses, myocardial ischemia and infarct sizes were evaluated using Evans blue/TIC staining, myocardial apoptosis were analyzed by TUNEL staining and the activities of Caspase-3, 8, 9. Results （1）Compared with the MI/R group, the protein levels of HIF-1α were increased almost 4.6 folds in the D＋MI/R group, while CK-MB and LDH levels in the serum were decreased （P〈0.05）, the infarct size was reduced （P〈0.05） and histological injury was significantly decreased. （2）Compared with the MI/R group （23.5±1.5）%, the rate of the myocardial apoptosis was significantly decreased in the I）MI/R group [ （9.7±0.98）% ,P〈0.05）], with partially counteracted the increase of Caspase-9 and Caspase-3 activities（P〈0.05）. Conclusion The stable expression of HIF-1α have an anti-apoptotic effect on myocardial ischemia-reperfusion injury, which mediated by mitochondria pathway.

关 键 词：低氧诱导因子-1Α 心肌 缺血再灌注损伤 细胞凋亡 

分 类 号：Q95-33[生物学—动物学] R542[医药卫生—心血管疾病]