二甲双胍治疗坐骨神经结扎诱发大鼠神经病理性疼痛的效应  

Effect of metformin for treatment of neuropathic pain induced by sciatic nerve chronic constriction injury in rats

作　　者：王之遥 李瑋珊 李艾伦 方芳 仓静 WANG Zhi-yao;LI Wei-shan;LI Ai-lun;FANG Fang;CANG Jing(Department of Anesthesiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院麻醉科,上海230032

出　　处：《中国临床医学》2019年第2期200-204,共5页Chinese Journal of Clinical Medicine

基　　金：复旦大学附属中山医院青年基金(2016ZSQN62)~~

摘　　要：目的:探讨二甲双胍治疗坐骨神经慢性压迫损伤(chronic constriction injury,CCI)诱发大鼠神经病理性疼痛的效应。方法:SPF级健康雌性SD大鼠48只,7～9周龄,180～200 g,采用随机数字表法将其分为正常对照组(Naive组)、假手术组(Sham组)、CCI组和CCI+二甲双胍组(Met组),每组12只。二甲双胍采用灌胃方式给药,每次剂量45 mg/kg,从CCI建模前3 d开始给药,每天2次,持续至建模后第7天。分别于建模前(基线水平),术后3 d、7 d、10 d、14 d记录建模侧(左侧)后足机械缩足反射阈值(MWT)、热缩足潜伏期(TWL)和冷刺激诱发缩足次数(TNCW);第3、14天使用CatWalk步态分析系统测定各组大鼠的步态。结果:与Naive组比较,CCI组和Met组大鼠左足MWT降低、TWL缩短、TNCW减少(P<0.05);CCI组大鼠左侧足印面积缩小、完整足印的平均强度减弱、站立时间缩短、步周长减小、摆动时间延长,并持续至建模后第14天(P<0.05);Met组大鼠左侧足印面积缩小、完整足印的平均强度减弱;Sham组上述指标无明显改变。与CCI组相比,Met组大鼠左足MWT升高、TWL延长、TNCW增加(P<0.05); Met组大鼠左侧足印面积增大、完整足印的平均强度增强、站立时间延长以及步周长增加(P<0.05),摆动时间无明显改变。结论:二甲双胍可缓解CCI诱发神经病理性疼痛大鼠机械痛觉过敏和冷热痛觉过敏,且能改善神经病理性疼痛大鼠的步态。Objective:To evaluate the effect of metformin for treatment of neuropathic pain induced by sciatic nerve chronic constriction injury in rats.Methods:Forty-eight female SPF Sprague-Dawley rats(age,7-9 weeks;weight,180-200 g)were randomly divided into 4 groups(n=12 in each group):control group(Naive group),sham operation group(Sham group),CCI group and CCI+metformin group(Met group).Metformin(45 mg/kg,2 times every day)was administrated orally from 3 d before to 7 d after operation.The left mechanical paw withdrawal threshold(MWT),thermal paw withdrawal latency(TWL),and number of cold stimulated paw withdrawal were measured before operation(baseline)and 3 d,7 d,10 d,14 d after operation.CatWalk analysis system was used to measure the change in gait of rats in all groups 3 d and 14 d after operation.Results:Compared with the Naive group,the left MWT,TWL,and TNCW decreased in the CCI and Met groups(P<0.05).Compared with Naive group,print area,mean print intensity,stand time,and stride length of left paw of rats decreased,but swing time increased in the CCI group,and continued to 14 d after operation(P<0.05);The print area,mean print intensity decreased in the Met group;above indexes in the Sham group were unchanged.Compared with the CCI group,the left MWT,TWL,and TNCW increased in Met group(P<0.05).Compared with the CCI group,the print area,mean print intensity,stand time,stride length of left paw of rats improved in the Met group(P<0.05),but the swing time was unchanged.Conclusions:Metformin can alleviate mechanical hyperalgesia,thermal and cold allodynia in rats with CCI-induced neuropathic pain,and can improve the gait of rats with neuropathic pain.

关 键 词：神经病理性疼痛 慢性压迫损伤 二甲双胍 大鼠 

分 类 号：R977.15[医药卫生—药品]