丁咯地尔对坐骨神经损伤大鼠背根神经元凋亡及caspase-3表达的影响  

Effects of buflomedil on apoptosis and expression of caspase-3 in dorsal root ganglion neurons in rats of sciatic nerve lesion model

作　　者：苏建华[1] 章莉萍[1] 陈玉芳[2] 唐金荣[3] 肖杭[4] 包德诚[1] 

机构地区：[1]江苏大学附属金坛医院神经内科,江苏金坛213200 [2]常州市第四人民医院病理科,江苏常州213001 [3]南京医科大学第一附属医院神经内科,江苏南京210029 [4]南京医科大学应用神经毒理研究所,江苏南京210029

出　　处：《中国新药与临床杂志》2010年第5期369-372,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：江苏省常州市科技局指导性科研项目(2008928);金坛市科技局资助项目(TS2007069);金坛市133工程资助项目(2008)

摘　　要：目的研究丁咯地尔对大鼠坐骨神经损伤后背根神经元凋亡及半胱氨酸天冬氨酸蛋白酶3(caspase-3)表达的影响。方法将84只成年健康Sprague-Dawley大鼠随机分为3组(n=28),除正常组外,模型组和丁咯地尔组大鼠分别腹腔注射生理盐水和丁咯地尔40 mg.kg-1.d-1,共14 d,然后制作坐骨神经损伤动物模型。分别在手术后6、12、24、48、72、96 h和7 d提取L1-5背根神经节。用原位末端脱氧核糖核酸转移酶介导的脱氧尿苷三磷酸(dUTP)标记法(TUNEL法)检测神经细胞的凋亡水平,用免疫组化方法检测caspase-3阳性表达细胞。结果正常组大鼠背根神经细胞凋亡和caspase-3阳性细胞较少;而模型组在坐骨神经损伤后12 h,出现大量神经细胞凋亡及caspase-3阳性表达(P<0.01),72 h达高峰,96 h后有下降趋势;丁咯地尔组在坐骨神经损伤后12 h也出现大量神经细胞凋亡及caspase-3阳性表达(P<0.01),但较同期模型组明显减少(P<0.05,P<0.01)。结论坐骨神经损伤后背根神经元存在广泛的细胞凋亡现象,丁咯地尔通过抑制caspase-3蛋白表达从而抑制细胞凋亡,发挥其神经保护作用。AIM To study the effects of buflomedil on the apoptosis and the changes of caspase-3 expression in dorsal root ganglion neurons in rats of sciatic nerve lesion model.METHODS Eighty-four SD rats were randomly divided into 3 group（n = 28）,except for the normal group,the model group and the buflomedil group was received normal saline and buflomedil 40 mg.kg-1.d-1 respectively for 14 d,then the sciatic nerve lesion models were performed.The apoptosis of the dorsal root ganglion neurons were detected by TUNEL method and the expression of caspase-3 were detected by immunohistochemical method 6,12,24,48,72,96 h,and 7 d after the operation,respectively.RESULTS There was less TUNEL-positive cells and caspase-3 expression in normal group.After 12 h of the model operation,the apoptosis and caspase-3 expression in model group increased obviously（P 0.01）,peaked at 72 h,and decreased from 96 h.The apoptosis and the expressions of caspase-3 in buflomedil group also increased（P 0.01） 12 h after the sciatic nerve lesion,but less than those of model group（P 0.05 or 0.01）.CONCLUSION There are a number of neuron apoptosis in dorsal root ganglion after sciatic nerve lesion,buflomedil can down-regulate the expression of caspase-3 to perform the neuro-protective effect by inhibiting apoptosis.

关 键 词：丁咯地尔 坐骨神经 神经节 脊 细胞凋亡 半胱氨酸天冬氨酸蛋白酶3 

分 类 号：R972[医药卫生—药品] R961[医药卫生—药学]