甲钴胺对脑缺血-再灌注大鼠皮层神经细胞凋亡的预防作用  

Preventive effect of methycobal on apoptosis of brain tissue in rats with cerebral ischemia-reperfusion injury

作　　者：苏建华[1] 陈玉芳[2] 肖杭[3] 林伟[1] 

机构地区：[1]江苏大学附属金坛医院神经内科,213200 [2]常州市第四人民医院病理科 [3]南京医科大学应用神经毒理研究所

出　　处：《江苏医药》2015年第10期1135-1138,F0003,共5页Jiangsu Medical Journal

基　　金：江苏省"333高层次人才培养工程"科研项目(BRA2012050);江苏大学医学临床科技发展基金(JLY2010053);常州市科技局资助项目(WZ201043)

摘　　要：目的探讨甲钴胺对缺血-再灌注(I-R)大鼠大脑皮层神经细胞凋亡的影响。方法Wistar大鼠135只随机均分为五组:A组为空白对照;B、C、D和E组分别用0.9%氯化钠20ml·kg-1·d-1、尼莫地平1mg·kg-1·d-1、甲钴胺50μg·kg-1·d-1和100μg·kg-1·d-1灌胃1周后建立脑I-R模型。观察再灌注24h后神经功能缺损评分。再灌注6、12和24h,用TUNEL法检测大脑皮层细胞凋亡,Western blot检测大脑皮层半胱氨酸天冬氨酸酶3(Caspase-3)蛋白表达。结果再灌注24h后,C、E组神经功能评分低于B、D组(P<0.05或P<0.01)。C、D和E组神经细胞凋亡数均少于B组,E组少于D组(P<0.01)。C、D和E组大脑皮层Caspase-3表达均低于B组,D组高于C组(P<0.01)。结论预用甲钴胺对大鼠脑I-R损伤有保护作用,可能与抑制大脑组织Caspase-3蛋白表达有关。Objective To investigate the preventive effect of methycobal on apoptosis of brain tissue in rats with cerebral ischemia-reperfusion（I-R） injury. Methods A total of 135 Wistar rats was equally randomized into 5 groups of A（blank control）, B（treated with normal saline）, C（treated with nimodipine 1 mg ·kg^-1·d^-1 ）,D（treated with methycobal 50μg·kg^-1·d^-1） and E（treated with methycobal 100μg·kg^-1·d^-1）. The drugs were used by gastric gavage for eontinous 7 days. Then cerebral I-R models were established by middle cerebral artery occlusion for 3 hours in groups of B, C, D and E. Neurological deficit scores were evaluated at 24 h after reperfusion. The apoptosis of perifocal cortex was analyzed by TUNEL method and the expression of Caspase-3 was detected by Western blot at the end of 6,12 and 24 hours after reperfusion. Results Neurological deficit scores at 24 hours after reperfusion were lower in groups of C and E than those in groups of B and D（P〈O. 05 or P〈0. 01）. The numbers of cortex cell apoptosis were less in groups of C, D and E than those in group B, which were less in group E than those in group D（P〈0. 01）. The expressions of Caspase-3 in the cortex tissues were lower in groups of C, D and E than those in group B（P〈0. 01）, which were higher in group D than those in group C（P〈0. 01）. Conclusion Preventive use of methycobal has a protective effect on cerebral I-R injury in rats, which is probably related to an inhibition of Caspase-3 expression in cerebral tissues.

关 键 词：甲钴胺 脑缺血-再灌注损伤 凋亡 半胱氨酸天冬氨酸蛋白酶3 

分 类 号：R972[医药卫生—药品]