二苯乙烯苷对脑缺血再灌注大鼠神经保护的作用机制  

Neuroprotective mechanism of tetrahydroxystilbene glucoside on rats after cerebral ischemia-reperfusion

作　　者：杨杰[1] 周芝文[1] 杨期东[1] 郑丽君[1] 曾进[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410078

出　　处：《中南大学学报（医学版）》2010年第4期321-328,共8页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(08JJ3083)~~

摘　　要：目的:探讨二苯乙烯苷(tetrahydroxystilbene glucoside,TSG)对脑缺血再灌注大鼠的神经保护作用机制。方法:雄性SD大鼠96只,随机分为4组:对照组,模型组,小剂量[60mg/(kg·d)]TSG组,大剂量[120mg/(kg·d)]TSG组,每组24只。TSG或生理盐水灌胃7d后应用线栓法制备大鼠大脑中动脉缺血再灌注损伤模型,术后6,24,48h及7d观察动物神经行为学变化并评分,免疫组织化学法检测神经生长因子(NGF)、生长相关蛋白(GAP)-43和蛋白激酶A催化亚基(PKAc)蛋白的表达。结果:神经功能评分显示模型组各时间点均有明显的神经功能缺损症状,除6h时间点外,两个剂量TSG治疗组其余各时间点神经功能评分明显低于模型组,差异有统计学意义(P<0.05);与模型组相比,两个剂量TSG组各时间点NGF,GAP-43及PKAc蛋白表达均升高,差异有统计学意义(P<0.01)。NGF,GAP-43及PKAc蛋白表达两两之间呈正相关。结论:TSG可能通过诱导大鼠脑缺血-再灌注损伤后NGF蛋白表达上调,激活PKA通路,增加轴突再生标志物GAP-43蛋白的表达,从而起到神经保护作用。Objective To investigate the neuroprotective mechanism of tetrahydroxystilbene glucoside （TSG）,a Chinese medicine,on rats after cerebral ischemia-reperfusion.Methods A total of 96 Sprague-Dawley male rats were divided into 4 groups （n=24）：a control group,an ischemia-reperfusion （I/R） model group,a low dose TSG [60 mg/（kg·d）]group,and a high dose TSG [120 mg/（kg·d）]group.After 6 days intragastric（ig） administration of TSG or natural saline （I/R group）,reversible middle cerebral artery occlusion （MCAO） model was established by intraluminal suture technique.The rats of control group were operated on while the middle cerebral artery was not blocked.At 6 h,24 h,48 h,and 7 d after the reperfusion,behavior test was used to evaluate the neurological deficiency of each group.The protein expressions of nerve growth factor （NGF）,growth associated protein （GAP）-43,and protein kinase A catalytic subunit （PKAc） in the cortex were measured by immunohistochemical method.Results Compared with the I/R group,the neurological defect scores of the 2 TSG groups were significantly lower except at 6 h after the reperfusion.Compared with the I/R group,the protein expression of NGF,GAP-43,and PKAc after the reperfusion of the 2 TSG groups increased significantly.Conclusion The protein expression of NGF may increase when treated with TSG after cerebral ischemia-reperfusion,which activates the PKA pathway and increases the protein expression of GAP-43 that protects the neuron.

关 键 词：二苯乙烯苷 脑缺血再灌注 神经生长因子 生长相关蛋白-43 蛋白激酶A催化亚基 

分 类 号：R285.5[医药卫生—中药学]