自由基清除剂联合钙离子拮抗剂对脑缺血神经元凋亡的影响

摘要/Abstract

摘要：

【摘要】目的观察自由基清除剂联合钙离子拮抗剂对大鼠脑缺血半暗带神经元凋亡及B细胞淋巴瘤/白血病-2（B cell lymphoma/leukemia-2，Bcl-2）和Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）表达的影响。方法线栓法制备大鼠大脑中动脉缺血再灌注模型，随机分为假手术组、对照组和干预组，干预组又分为自由基组、钙离子组及联合干预组。对照组及各干预组根据缺血再灌注时间分为再灌注6 h、24 h、48 h、72 h及5 d组，每组各16只大鼠。对照组大鼠每日腹腔注射3 mg/kg生理盐水及灌胃给服12 mg/kg淀粉，自由基组大鼠每日腹腔注射3 mg/kg依达拉奉，钙离子组大鼠每日灌胃给服12 mg/kg尼莫地平，联合干预组大鼠每日腹腔注射3 mg/kg依达拉奉及灌胃给服12 mg/kg尼莫地平。观察各组大鼠缺血侧脑梗死面积、缺血半暗带Bcl-2、Bax蛋白表达及神经元凋亡的变化。结果缺血再灌注后6 h，各干预组与对照组比较，大鼠缺血侧脑梗死面积、脑缺血半暗带神经元凋亡及凋亡相关Bcl-2、Bax蛋白表达差异无显著性（P均>0.05）；缺血再灌注后48 h、72 h和5 d，与同时间段对照组比较，各干预组大鼠脑缺血半暗带区Bcl-2蛋白表达增强，Bax蛋白表达降低，凋亡神经元数减少，梗死区面积缩小，差异有显著性（P均＜0.05）；与自由基组及钙离子组比较，联合干预组大鼠上述指标改变更显著，差异有显著性（P均＜0.001）；自由基组与钙离子组组间比较，上述各指标差异无显著性（P均>0.05）。结论在脑缺血再灌注损伤中，联合应用自由基清除剂和钙离子拮抗剂对缺血半暗带神经元具有较好的协同保护作用。

关键词: 缺血再灌注; 缺血半暗带; 联合干预; 凋亡

Abstract:

【Abstract】 Objective To observe the combined effects of free radical scavenger Edaravone and calcium antagonist Nimodipine on neuronal apoptosis and related apoptotic protein Bcl-2 and Bax expression in the cerebral ischemic penumbra perifocal regions of brains after cerebral ischemia. Methods Transient middle cerebral artery occlusion(tMCAO) rat models were established by using Longa's suture insertion. Adult male Wistar rats(n=336) were randomly divided into sham-operated, control group, Edaravone-treated group, Nimodipine-treated group and co-treated group. Animals underwent 2 hours of tMCAO and 0.25, 1, 2, 3 and 5d reperfusion with 16 rats in each group. From ischemia-reperfusion 5h to the time when brains were removed, The rats of control group received intraperitoneal injection of 3mg/kg physiological saline and oral administration 12mg/kg starch daily, The rats of Edaravone-treated group received intraperitoneal injection of 3mg/kg Edaravone daily, The rats of Nimodipine-treated group received oral administration 12mg/kg Nimodipine daily, The rats of co-treated group received intraperitoneal injection of 3mg/kg Edaravone and oral administration 12mg/kg Nimodipine daily. The infarct area of the ischemic brain, Bcl-2 and Bax expression, and TUNEL staining in the ischemic perifocal region were examined after tMCAO in these groups.

Results Ischemia-reperfusion 6h, there is no statistical significant between Edaravone-treated group, Nimodipine-treated group, co-treated group and control group of Bcl-2 positive cells, Bax positive cells, apoptotic cells of the ischemic penumbra and the infarct area(P>0.05). Ischemia-reperfusion 48h, 72h and 5d, Compared to the control group, Bcl-2 positive cells was greatly increased in the ischemic perifocal region in the Edaravone-treated group, Nimodipine-treated group, and co-treated group, while the Bax positive cells and apoptotic cells decreased. In addition, the infarct area attenuated, there was statistical significant of above results(P＜0.05). There was no statistical significant of results between the Edaravone-treated and Nimodipine-treated groups(P>0.05). Interestedly, co-treated group appeared recovered much better then signal treated group(P＜0.001). Conclusion The combination of free radical scavengers and calcium antagonist treatment may play a better coordination neuroprotective role on the ischemic neurons after tMCAO.

Key words: Cerebral ischemia-reperfusion; Penumbra; Combined intervention; Apoptosis

黄浩，李吕力，张丽香，罗永坚，肖继东，陈渊，唐士婷，蔺心敬. 自由基清除剂联合钙离子拮抗剂对脑缺血神经元凋亡的影响[J]. 卒中杂志, 2012, 7(12): 922-929.

HUANG Hao, LI Lv-Li, ZHANG Li-Xiang, LUO Yong-Jian, XIAO Ji-Dong, CHEN Yuan, TANG Shi-Ting, LIN Xin-Jing.. Effects of Radical Scavengers Joint Calcium Antagonists on Neuronal Apoptosis[J]. Chinese Journal of Stroke, 2012, 7(12): 922-929.

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