吡格列酮对大鼠缺血再灌注诱导的内质网应激相关的心肌保护作用  

Endoplasmic reticulum stress-related protective effect of pioglitazone on the myocardium with ischemia-reperfusion injury

作　　者：李艳[1] 范学秀[1] 王妍妍[1] 

机构地区：[1]山西医科大学第一临床医学院心血管内科,太原市030001

出　　处：《中国心血管病研究》2013年第5期376-379,I0002,共5页Chinese Journal of Cardiovascular Research

基　　金：山西省大学生创新创业专题项目（项目编号：120164070）

摘　　要：目的观察吡格列酮对大鼠心肌缺血再灌注损伤（MIRI）时JNK、p-JNK及caspasc-12蛋白表达的影响，探讨吡格列酮通过JNK通路对内质网应激途径的心肌保护作用。方法Wistar大鼠40只随机分为假手术组（sham组）、缺血再灌注组（I／R组）、I／R＋Pio（吡格列酮）组及I／R＋Pi0＋sP600125组各10只。制作大鼠MIRI模型；TUNEL检测心肌细胞凋亡，免疫组织化学检测各组caspase-12表达变化，westernBlot法检测各组JNK、P-JNK的表达。结果吡格列酮预处理组大鼠心肌细胞凋亡、JNK磷酸化率及caspase-12蛋白表达水平明显比I／R组降低（P〈0．05），加用JNK抑制剂（SP600125）后上述指标进一步下降，与吡格列酮组比较差异有统计学意义（P〈0．05）。结论缺血再灌注损伤可激活JNK通路，诱导过度的ERS，增加ER凋亡信号介导的细胞凋亡。吡格列酮预处理可减少ER凋亡信号介导的细胞凋亡，JNK信号途径在吡格列酮预处理抑制ER凋亡信号分子活化的机制中发挥重要作用。Objective To observe influence of pioglitazone on the expression of JNK/p-JNK and cas- pase-12 in ischemia-reperfusion in rats, and discuss the myocardial protective effect of pioglitazone to the endo- plasmic reticulum stress way through the JNK pathway. Methods Forty rats were randomly divided into four groups： sham operation group （n=10）, ischemia-reperfusion group （n=10）, pioglitazone 10 mg treated group （n= 10）, pioglitazone 10 mg treated and SP600125 group （n=10）. Left anterior descending coronary artery was ligated for 30 min and reperfused for 2 hour to establish the model of ischemia-reperfusion. TUNEL was performed to de- tect apoptosis of myocardial cells, immunohistochemistry was performed to detect the expression of caspase-12, Western blot was performed to detect the expression of JNK and p-JNK. Results The apoptosis index and the ex- pression of caspase-12 and the expression of p-JNK in ischemia-reperfusion group increased after ischemia-reper- fusion compared with sham operation group and pioglitazone treatment reduced the above index, SP600125 augment- ed the reducing effect. Conclusion Ischemia-reperfusion can activate JNK access and induce severe ER then ag- gravate cell apoptosis induced by ERS. Pioglitazone could reduce the myocardial apoptosis induced by ERS, which are important protection factors are mediated by JNK.

关 键 词：心肌血再灌注损伤 C-JUN氨基末端激酶 内质网应激 吡格列酮 

分 类 号：R542.2[医药卫生—心血管疾病]