脑心通对大鼠脑缺血损伤的保护机制

The protective mechanism of Naoxintong on cerebral ischemic injury in rats

目的:观察脑心通对大鼠缺血脑组织(纹状体)葡萄糖调控蛋白78(glucose-regulated protein 78,GRP78)、GRP94表达的影响,探讨其对大鼠局灶性脑缺血损伤可能的保护机制。方法:大鼠随机分为假手术组、缺血损伤组(线栓法制备大鼠局灶性脑缺血模型)以及脑心通治疗组(缺血损伤前予脑心通治疗,n=30)。应用组织学观察、免疫组织化学及半定量RT-PCR检测缺血不同时段(6、12、24 h)各组大鼠纹状体GRP78、GRP94表达的变化。结果:成功建立大鼠局灶性脑缺血模型。组织学观察表明脑心通治疗组大鼠脑缺血损伤程度较缺血损伤组明显减轻。免疫组织化学检查和RT-PCR检测均发现各时间点假手术组大鼠纹状体GRP78、GRP94表达高于缺血损伤组(P<0.01);缺血后6、12、24 h缺血损伤组、脑心通治疗组GRP78、GRP94表达呈现先升高后降低趋势,缺血后12 h的表达最高;各时间点缺血损伤组GRP78、GRP94表达低于脑心通治疗组(P<0.05或P<0.01)。结论:大鼠纹状体缺血损伤后12 h内出现GRP78、GRP94表达升高;脑心通能够提高脑缺血损伤组织GRP78、GRP94表达;脑心通可能是通过促进GRP78、GRP94表达来发挥保护内质网功能,减轻脑缺血损伤。

Objective：To observe the influence of Naoxintong on expression of glucose-regulated protein 78（GRP78） and GRP94 in the striatum of rats with focal cerebral ischemic injury, so as to investigate their possible protective mechanism on cerebral ischemic injury. Methods： Ninety rats were equally randomized into 3 groups（n= 30）： sham operated group, ischemic group （Focal transient cerebral ischemia model was established with intraluminal occlusion of left middle cerebral artery） and Naoxintong pre-treated group （Treated with Naoxintong 5 d before ischemic injury）. The expression of GRP78, GRP94 in rats striatum was detected by histological method, immunohistochemistry staining and semiquantitative RT-PCR at the different time points（6,12 and 24 h after ischemic treatment）. Results： The focal transient cerebral ischemia model was successfully established in rats. Histological results showed that the degree of focal cerebral ischemic injury in Naoxintong pre-treated group was significantly lower than that in ischemic group. Immunohistochemistry staining and RT-PCR results illustrated that the expression of GRP78 and GRP94 in ischemic group was lower than that in sham operated group at each time point after ischemic treatment （P〈0.01）. The expression of GRP78 and GRP94 in ischemic group and Naoxintong pre-treated group were the lowest at 6 h and the highest at 12 h, and the expression at 24 h was lower than that at 12 h but higher than that at 6 h. Compared with the ischemic group, the expression of GRP78 and GRP94 was higher in Naoxintong pre-treated group at the same time point （P〈 0.05, P〈0.01）. Conclusion：The expression of GRP78 and GRP94 is upregulated within 12 h of cerebral i schemic injury in rats. Naoxintong can promote the expression of GRP78 and GRP94 in ischemic cerebral areas, protect the function of endoplasmic reticulum and relieve the cerebral injury caused by ischemia.