缺氧诱导因子1 alpha在急性心肌缺血中的表达规律

Regularity of Hypoxia-inducible Factor 1 Alpha Expression in Acute Myocardial Ischemia

目的研究心肌缺血状态下HIF-1α的表达规律及其在死亡之后48h的动态变化。方法建立SD大鼠急性心肌缺血模型。随机将大鼠分为正常对照组、假手术组、急性心肌缺血试验组和窒息组。用免疫组化、RT-PCR和Westernblot检测心肌缺血及死亡后HIF-1α的表达规律。结果术后30min缺血心肌中开始出现HIF-1αmRNA表达上调,4～6h达高峰,至术后48h仍维持此高水平;蛋白质的表达相对滞后,于术后2h开始被检测到,之后表达进行性上升,至12h达高峰后维持在高水平;其它各组HIF-1α检测均为阴性。大鼠术后48h处死,死亡后48h内均可检测到HIF-1αmRNA和蛋白质的表达,但表达呈进行性下降趋势;其他各组均未检测到HIF-1α表达。结论HIF-1α可作为一个早期心肌缺血的敏感的辅助诊断指标,并用于急性心肌缺血缺氧性死亡和其他原因(例如窒息)缺氧造成的死亡的鉴别。

[Objective] This study was to observe the regularity of HIF-1α expression in acute myocardial ischemia and its dynamic changes after death in 48 hours. [Methods] SD rats were used to build the animal model of acute myocardial ischemia. The rats were randomly divided into normal control group, pseudo surgery group, surgery group and asphyxia group. Immunohistochemistry, RT-PCR and Western blot were used to investigate the expression of HIF-1α. [Results] The expression of HIF-1α mRNA was began to elevate obviously in ischemic cardiac muscle at 30 min after surgery and reached its peak at about 4-6 hours. Till 48 hours after surgery, the expression still maintained this level. The expression of HIF-lctprotein lagged behind the mRNA. The protein was begun to be detected at 2 hours after surgery. Its level increased gradually and reached its peak at 12 hons after surgery and maintained this level. The expression of HIF-1α could not be detected in the other groups. The animals were killed at 48 hours after surgery. The mRNA and protein of HIF-1α could be detected till 48 hours after death. Their levels decreased gradually. The expression of HIF-lct could not be detected in the other group. [Conclusions] HIF-la was a sensitive marker for early acute myocardial ischemJa and could be used to help the diagnosis of sudden death due to acute myocardial ischemia. It could also be used to distinguish the sudden death causes between acute myocardial ischemia and others such as asphyxia.