乐尔脉对脑缺血再灌注神经细胞凋亡与相关基因表达的影响  

Influence of Leermai on neuronal apoptosis and chain related genes expression in brain ischemia reperfusion injured rats

作　　者：王胜春[1] 李剑锋[1] 王俊琴[1] 刘明义[1] 田卫斌[1] 

机构地区：[1]第四军医大学西京医院药剂科,陕西西安710032

出　　处：《中成药》2009年第3期358-363,共6页Chinese Traditional Patent Medicine

摘　　要：目的:探讨脑缺血再灌注损伤后皮层神经细胞凋亡与相关基因表达及乐尔脉(当归,莪术等)的作用与机制。方法:采用大鼠左侧大脑中动脉内栓线阻断法造成局灶性脑缺血再灌注模型。缺血2 h再灌注3 d后,应用原位末端标记法(TUNEL)检测皮层神经细胞凋亡。免疫组化、RT-PCR法检测皮层神经细胞Fas、Fas-L、Bax、BcL-2、Caspase-3、9蛋白及mRNA的表达。结果:大鼠缺血2 h再灌注3 d后,模型组缺血侧皮层细胞凋亡率显著高于假手术组(P<0.01),凋亡相关蛋白Fas、Bax、Caspase-3、9表达区域与凋亡一致,凋亡相关基因Fas、FasL、Bax、Caspase-3、9mRNA的表达上调(P<0.05)。LEM 2.0 g/kg、0.87 g/kg和氟桂利嗪可明显减少皮层神经细胞凋亡,下调Fas、Fas-L、Bax、Caspase-3、9mRNA的表达(P<0.05),LEM 0.87 g/kg作用次于2.0 g/kg。氟桂利嗪下调Bax mRNA和BcL-2 mRNA,乐尔脉既抑制Bax mRNA表达又上调BcL-2 mRNA。结论:乐尔脉抑制了神经细胞的凋亡,从而缓解了脑缺血再灌注后的损伤,这种脑保护作用与LEM对神经细胞凋亡信号转导通路蛋白及相关基因调节作用有关。AIM： To investigate the apoptosis and related genes expression in brain cortex tissue after brain ischemia reperfusion injured rats as well as the effects and mechanism of Leermai（ Radix angelicae sinensis, Rhizoma curcumae, etc. ） （LEM）. METHODS ： A rat middle cerebral artery occlusion reperfusion model were established by the use of the intraluminal filament. During reperfusion for 3 d after ischemia 2 h, the TUNEL Tagger was used to detect cortical cell apoptosis, eosinnophillic change of cortical cell were observed with HE staining, the immunohistochemical and RT-PCR technique were used to assay the expression of Fas, Fas-L, Bax, Bcl-2, Caspase-3, 9 protein as well as mRNA. RESULTS： Compared with sham operation group, after 2 h ischemia and 3 d reperfusion, TUNEL positive cell increased markedly in cortex, and the expression site of Fas, Bax, Caspase-3, 9 protein were consistent with distribution of cortical cell apoptosis and also were consistent with distribution of eosinnophillic change of cortical cell in cerebral cortex, and the expression of Fas mRNA, Fas-L mRNA, Bax mRNA, Caspase-3, 9 mRNA in cortex were significantly up-regnlated. Compared with model group, LEM and Flunarizinum group reduced significantly the apoptosis of cortical cell, and the expression of Fas mRNA, Fas-L mRNA, Bax mRNA, caspase-3, 9 mRNA in cerebral cortex were obviously down-regulated, such effect in LEM 0.87 g/kg was less than 2 g/kg group, Flunarizinum down-regulated the expression of Bax mRNA and BcL-2 mRNA, while LEM could not only down-regulate the expression of Bax mRNA but also up-regulate BcL-2 mRNA in cortex. CONCLUSION： LEM could inhibit the apoptosis of cerebral cells and relieve consequently the damage to cortical cell after cerebral ischemical reperfusion. The protective effects of LEM may be related to regulate the signal pathway related gene expression of neuronal apoptosis.

关 键 词：乐尔脉 脑缺血-再灌注 凋亡信号通路 

分 类 号：R285.6[医药卫生—中药学]