p38／Fas／FasL对心肌缺血再灌注损伤诱导细胞凋亡的调控作用

目的探讨p38／Fas／FasL对大鼠心肌缺血再灌注损伤诱导细胞凋亡的调控作用。方法SD大鼠20只随机分成2组（假手术组、模型组），每组10只。结扎冠状动脉左前降支，30min后剪断结扎线制作心肌缺血再灌注模型。对心肌组织进行苏木精一伊红（H—E）染色，观察心肌组织病理变化；免疫印迹（WesternBlotting）检测Fas、Fas配体（FasL）、p38促分裂素原活化蛋白激酶（p38MAPK）以及磷酸化p38MAPK（P—p38MAPK）在缺血再灌注心肌组织中的表达；TdT介导的dUTP缺口末端标记技术（TUNEL）法检测心肌细胞凋亡模型。结果H—E染色结果显示，模型组心肌纤维变性；Western Blotting结果显示模型组大鼠心肌组织中Fas、FasL、p38MAPK及P—p38MAPK蛋白的表达明显增高；TUNEL结果显示模型组的心肌组织中细胞凋亡明显增多。结论心肌缺血再灌注时Fas、FasL、p38MAPK和P—p3SMAPK表达明显增多，且与细胞凋亡率呈正相关，提示心肌缺血再灌注损伤诱导的心肌细胞凋亡可能是通过激活Fas／FasL／p38MAPK途径实现的。

Effect of p38/Fas/FasL on apoptosis in rats with myocardium ischemia/reperfusion injury

Objective To investigate the effects of p38/Fas/FasL on myocardial apoptosis in rats with ischemia/ reperfusion injury. Methods Twenty male Sprague - Dawley rats were selected and randomly divided into two groups （ n = 10 each） ： ① Sham - operated group ; ②ischemia./reperfusion （I/R） group. The myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary artery for 30 rain followed by 2 h reperfusion. The cardiac muscle tissue was stained by hematoxylin and eosin （ H - E ） to observe its pathological changes. Western blotting was used to detect the expression of Fas/FasL/p38 MAPK/p - p38 MAPK. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect the cardiomyocytc apoptosis. Results H - E staining showed that cardiac muscle cells were degenerated in I/R group. Western blotting showed that the expressions of Fas/FasL/p38 MAPK/p-p38 MAPK were significantly higher in ischemic area in the IR group compared to sham-operated group （P〈0.01）. TUNEL result showed that apoptotic cells increased in I/R group compared to sham -operated group （P 〈 0.01 ）, Conclusion Fas/FasL/p38 MAPK/p -p38 MAPK are expressed aboundantly following myocardial ischemia/ reperfusion and the expressions are positively correlated with apoptosis rate. The results suggest that the mechanism of myocardial apoptosis induced by myocardial ischemia/reperfusion injury may be associated with the activation of Fas/ FasL/p38MAPK signal pathway.