缝隙连接胞间通讯对大鼠局灶性脑梗死体积的影响

Effect of astrocyte gap junction intracellular communication on focal ischemic stroke in rats

目的探讨缝隙连接胞间通讯变化对大鼠局灶性脑梗死体积的影响。方法Wistar大鼠随机分为4组,干预组术前腹腔注射缝隙连接特异性阻滞剂辛醇,对照组及假手术组给予等量生理盐水,溶剂对照组给予等量溶剂。线栓法建立大脑中动脉闭塞／再灌注模型。采用Longa5分制评分法评价动物神经功能缺损程度、TTC染色考察脑梗死体积变化并在光镜下观察其病理变化。结果在缺血24h和缺血6h／再灌注6h条件下,辛醇干预组脑梗死体积百分比与手术对照组比较明显减小(P<0．05)。镜下可见辛醇组缺血中心区及半影区面积均明显缩小,半影区病理改变较轻,相对面积比显著减少。两组动物神经功能缺损程度虽有差异,但不具有统计学意义(P>0．05)。结论星形胶质细胞的缝隙连接在缺血性卒中半影区的病变进展中扮演重要角色。抑制缝隙连接胞间通讯对半影区神经元起到了保护作用,减小了梗死体积。探索下调缝隙连接胞间通讯功能的方法可能成为治疗脑梗死的新思路。

Objective To identify the effect of astrocyte gap junction intracellular communication（GJlC） on focal ischemic stroke in rats. Methods Wistar rats were divided randomly into 4 groups,sham-operated group, control group,oetanol-treatment group and DMSO vehicle control group. The animals of sham-operated group and control group were injected normal saline intraperitoneally 30min before operation. The animals of octanol-treatment group were injected octanol solution and animals of DMSO group,DMSO vehicle only. MCAO/R model was induced by intraluminal suture technique first described by Longa with a little modification. Praxiology changes and neurologic impairment were evaluated by Longa＇s five-grade scoring standard. Infarction volume was calculated by TTC staining. Pathological changes were observed under microscope. Results Compared to control group,the octanol-treatment group showed significant smaller ratios of infarction volume under both ischemia and ischemia/ reperfusion conditions. The pathological changes of treatment group were also slighter than those of control. There was no difference in neurologic impairment between two ischemia subgroups of octanol-treatment group and control group. Conclusion GJIC of astrocyte may play an important role in progress of focal ischemic stroke. Blockade of astrocyte gap junctions can effectively decrease the infarction volume in MCAO/R animal model. Down-regulating astrocyte GJIC may have neuroprotective significance in focal ischemic stroke.