α-硫辛酸对脑缺血再灌注大鼠凋亡调控基因Bax和JNK3表达的影响  

Effect of alpha-lipoic acid injection on the expressions of apoptotic regulatory gene Bax and JNK3 in rats after cerebral ischemia reperfusion

作　　者：董银华[1] 张侃[2] 王洪新[1] 陈泽峰[1] 李强[1] 范宏光[1] 赵岚[1] 高路燕[1] 王利军[1] 

机构地区：[1]天津医科大学第四中心临床学院神经内科,300140 [2] 滨州医学院附属医院神经内科

出　　处：《中华老年医学杂志》2015年第4期426-430,共5页Chinese Journal of Geriatrics

摘　　要：目的 探讨α-硫辛酸对大鼠脑缺血再灌注损伤后脑组织凋亡调控基因Bax mRNA和JNK3蛋白表达的影响.方法 120只雄性SD大鼠分为假手术组,脑缺血再灌注组（模型组）,α-硫辛酸预干预组（干预组）,根据再灌注时间不同又分为6h、12h、24 h、48 h组.进行神经功能评分,脑梗死体积测定,利用原位杂交、免疫印迹（Western blot）法检测各组大鼠凋亡调控基因Bax mRNA和JNK3蛋白表达水平.结果 与假手术组比较,模型组、干预组在各时点凋亡细胞计数、凋亡调控基因Bax mRNA和JNK3蛋白的表达增高.干预组与模型组比较,可改善24 h、48 h神经功能缺损[（1.50±0.55）分比（2.33±0.52）分、（1.33±0.52）分比（2.00±0.63）分],减少各时点脑梗死体积（均P＜0.05）;降低12h、24 h、48 h促凋亡调控基因Bax mRNA表达及6h、12h、24 h、48 h时JNK3蛋白的表达（均P＜0.01）.结论 α硫辛酸注射液可抑制大鼠脑缺血再灌注后神经元凋亡,其抗凋亡机制可能与抑制Bax的表达和阻断丝裂原活化蛋白激酶（MAPK）-JNK3通路有关.Objective To investigate the effects of alpha lipoic acid injection on the expressions of apoptotic regulatory gene Bax and JNK3 in rats after cerebral ischemia reperfusion.Methods The rat model of cerebral ischemia reperfusion was set up by modified Zea Longa thread-occlusion method.120 male SD rats were randomly divided into 3 groups：sham operation group,cerebral ischemia reperfusion group （model group） and alpha-lipoic acid pretreatment group.The rats in these groups were then divided into 4 subgroups according to the reperfusion time of 6h,12h,24h and 48h.The expression of apoptotic regulatory gene Bax after cerebral ischemia reperfusion was measured by the in situ hybridization.The protein expression of JNK3 was determined by Western blot.Results Compared with sham operation group,the expressions of Bax mRNA and JNK3 protein in the model group and alpha-lipoic acid pretreatment group were increased significantly at all time points.In alpha lipoic acid pretreatment group versus model group,the neurologic impairment score was improved at 24 h,48 h time points [（1.50±0.55） vs.（2.33±0.52）,（1.33±0.52） vs.（2.00±0.63）,both P 〈0.05] and the infarct volume were reduced at any time point （both P〈0.05）.The expressions ofBax mRNA at 12 h,24 h,48 h time points and JNK3 protein at 6 h,12 h,24 h and 48 h time points were lower in alpha-lipoic acid pretreatment group than in model group（all P〈0.01）.Conclusions Alpha lipoic acid injection decreases neuronal apoptosis in rat after cerebral ischemia reperfusion,and its anti apoptotic mechanism may be related with the inhibiting the apoptotic regulatory gene Bax mRNA expression and blockading the MAPK /JNK3 signal pathway.

关 键 词：脑缺血 再灌注损伤 凋亡 基因表达 

分 类 号：R965[医药卫生—药理学]