依达拉奉对糖尿病脑缺血再灌注大鼠细胞凋亡及缺氧诱导因子表达的影响

Effect on apoptosis and hypoxia inducible factor-1α expression of edaravone in diabetes cerebral ischemia/reperfusion model rats

目的探讨依达拉奉对糖尿病急性脑缺血再灌注大鼠细胞凋亡及缺氧诱导因子表达的影响。方法选取健康雄性SD大鼠70只,采用腹腔内一次性注入新鲜配制的1%链尿佐菌素(STZ)及线栓法建立糖尿病大鼠大脑中动脉闭塞再灌注模型。随机分成依达拉奉干预脑缺血再灌注组(干预组)30只、非依达拉奉干预脑缺血再灌注组(非干预组)30只、假手术组5只和正常组5只。前两组又分为缺血2h再灌注1h、6h、12h、24h、48h、72h亚组,每亚组5只。用TUNEL法检测细胞凋亡的变化,用免疫组化法检测缺氧诱导因子(HIF-1α)的表达水平。结果依达拉奉干预组各个时间点脑皮质区凋亡细胞数及缺氧诱导因子表达量均低于非依达拉奉干预组(P<0.05)。结论依达拉奉可明显减少糖尿病急性脑缺血再灌注大鼠脑神经细胞凋亡数,同时可减少缺氧诱导因子的表达。在糖尿病脑缺血再灌注过程中具有明显神经保护作用。

Objective To study the effects of edaravone on apoptosis and hypoxia inducible factor-1α expression in diabetes cerebral ischemia/reperfusion model rats.Methods 70 male SD rats were chosed randomly.Diabetic rat model of right middle cerebral artery occlusion （MCAO） was established by induction with strep tozocin （STZ） and line-lock method. The rats were randomly divided into four groups： edaravone dealed ischemic-diabetic group （the deal group,n=30）,nonedaravone dealed ischemia group （the nondeal group,n=30）,sham operation group （n=5）,and normal group （n=5）.The above two groups were subdivided into 6 subgroups randomly：1h,6h,12h,24h,48h and 72h subgroups after reperfusion following 2h ischemia （n=5）. And the apoptotic neurons of the rats were analyzed with TUNEL method.The expressions of hypoxia inducible factor-1α were evaluated by Western blotting.Results Compared with nonedaravone dealed ischemia group,less numbers of apoptotic neurons were detected in edaravone dealed ischemic-diabetic group at each reperfusion time（P0.05）.The expression of hypoxia inducible factor-1α in edaravone dealed ischemic-diabetic group were significantly lower compared with nonedaravone dealed ischemia group at each reperfusion time （P0.05）.Conclusion The injection of edaravone can obviously reduce apoptosis in diabetes ischemia/reperfusion model rats.At the same time, it can reduce the expression of hypoxia inducible factor-1α,which may obviously protect the neural injury in the diabetes cerebral ischemia/reperfusion.