大鼠急性心肌缺血早期缺氧诱导因子-1α的表达

Early Expression of Hypoxia-Inducible Factor-1 alpha after Acute Myocardial Ischemia in Rats

目的研究大鼠心肌缺血早期(6 h内)缺氧诱导因子-1α(hypoxia-inducible factor-1 alpha,HIF-1α)的表达规律及法医学意义。方法随机将SD大鼠分为正常对照组,假手术组,心肌缺血(结扎大鼠左冠状动脉前降支)15 min组、30 min组、1 h组、3 h组、6 h组。应用免疫组织化学染色、免疫荧光染色以及Western印迹法检测缺血心肌中HIF-1α的表达情况。结果正常对照组、假手术组未见HIF-1α的阳性表达;缺血15min组在心内膜下心肌中可见微弱的阳性表达;随着心肌缺血时间的延长,染色由心内膜下心肌逐渐向心外膜扩展,在3h左右达到高峰,6h左右有下降趋势但仍然维持在较高水平。部分大鼠左冠状动脉前降支结扎后,发生室性心律失常,在右心室可检测到HIF-1α阳性着色,分布于右心室全层且无时间规律性。结论 HIF-1α可作为早期心肌缺血所致心源性猝死的一个敏感鉴定指标,并可能有助于致死性心律失常的法医学鉴定。

Objective To observe the changes of hypoxia-inducible factor-1 alpha（HIF-1α）, the expression in the early stage （within 6h） of acute myocardial ischemia and to explore the potential forensic application. Methods SD rats were randomly divided into one control group, one sham operation group and five myocardial ischemia groups which received ligation of the left anterior descending（LAD） coronary artery. The five experiment groups divided into 15min, 30min, 1 h, 3 h and 6h after LAD ligation. The expression of HIF--1α was detected by immunohistochemistry, immunofluorescence and Western blotting, respectively. Results Both the control group and sham operation group showed no expression of HIF-1α, whereas the expression of HIF-1α could be weakly detected beneath the endocardium at 15 min after LAD ligation. With the increase of myocardial ischemia process, the positive staining gradually extended from endocardium to epicardium, reached the peak at 3 h, and began to decrease gradually at 6h after LAD ligation but still maintained at a relatively high level. In addition, the expression of HIF-1α without a time-dependent way was also detected in full thickness of the right ventricle in occurrence of ventricular arrhythmia after LAD ligation. Conclusion HIF-1α may be regarded as a sensitive marker for sudden cardiac death induced by early acute myocardial ischemia, and may also be helpful for the diagnosis of fatal arrhythmia.