亚低温对脑出血后非caspase酶依赖性凋亡通路的影响

The effect of mild hypothermia on expression of apoptosis inducing factor following intracerebral hemorrhage

目的观察亚低温对脑出血后非caspase依赖性通路中关键蛋白-凋亡诱导因子(apoptosis inducing factor,AIF)表达的影响。方法采用自体血注入法建立大鼠脑出血模型。将大鼠随机分为生理盐水组、脑出血组和脑出血+亚低温组。采用免疫组化法检测大鼠脑出血后24、72h及7d时血肿周围组织中AIF的表达;以Tunnel染色法观察各时间点神经细胞凋亡的变化。结果与生理盐水组比较,脑出血组Tunnel染色阳性细胞数和AIF表达高于生理盐水组(P<0.05)。同时,在脑出血组可以观察到Tunnel染色阳性细胞数和AIF表达在24h逐渐增加,72h达高峰(P<0.01)。亚低温组Tunnel染色阳性细胞数及AIF表达在各个时间点均低于脑出血组(P<0.05)。结论亚低温可能通过抑制脑出血后非caspase依赖性通路中的关键蛋白AIF的表达来减少神经元凋亡,发挥脑保护作用。

Objective To investigate the effect of mild hypothermia on the expression of apoptosis inducing factor （AIF） which was the key protein in caspase independent pathway after intracerebral hemorrhage （ICH）.Methods Male rats were randomly divided into three groups：the normal saline group,the ICH group,in which autologous arterial blood was stereotaxically injected into right caudate nucleus,the mild hypothermia group,in which the rats were given mild hypothermia after the injection of blood.The expression of AIF and apoptosis cells were assessed by immunostaining and TdT-mediated dUTP nick end-labeling （Tunnel）.Results Compared with the normal saline group,the expression of AIF and apoptosis cells were significantly higher in the ICH group.In the ICH group,the expression of AIF and apoptosis cells began to increase since 24 h after ICH and peaked at 72 h.Compared with ICH group,the expression of AIF and apoptosis cells markedly decreased in the mild hypothermia group,the result had significant difference （P＜0.05）.Conclusions Mild hypothermia can alleviate intracerebral hemorrhage damage of rats by inhibiting the expression of AIF which is the key protein in caspase-independent pathway.