钩吻素子抗糖尿病大鼠神经病理性疼痛的作用及其与脊髓别孕烯醇酮的关系  

Analgesic Effect of Koumine on Diabetic Neuropathic Pain in Rats and its Association with Spinal Allopregnanolone

作　　者：黄慧慧[1] 陈火树 钟志凤[1] 许盈[1] 俞昌喜[1] HUANG Huihui;CHEN Huoshu;ZHONG Zhifeng;XU Ying;YU Changxi(College of Pharmacy,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学药学院,福州350122

出　　处：《福建医科大学学报》2021年第1期14-18,共5页Journal of Fujian Medical University

基　　金：福建省自然科学基金(2018J01845,2019J01307);福建省新药研发中心Ⅱ期建设(2018L3008);福建省高校产学合作项目(2017Y4007);福建医科大学启航基金(2016QH016)。

摘　　要：目的观察钩吻素子对链脲佐菌素(STZ)所致糖尿病大鼠神经病理性疼痛(DNP)的镇痛作用,并观测其与脊髓别孕烯醇酮(AP)水平的关系。方法48只SD大鼠随机分为对照组(n=6)及STZ处理组(n=42)。根据血糖和机械刺激缩足阈(MWT),从STZ处理组筛选出成功制备DNP模型的动物,进一步随机分成5组:模型组、钩吻素子(0.28,1.4,7.0 mg/kg)处理组和加巴喷丁处理组。自STZ处理后第22天起,每只大鼠灌胃给予对应药物或溶剂,每天1次,持续8 d。以大鼠体质量和MWT为指标,观察钩吻素子对STZ处理的大鼠体质量和DNP的影响。待行为学实验结束后,ELISA法检测各组大鼠脊髓AP含量。结果钩吻素子对DNP大鼠的体质量无显著影响。与模型组比较,钩吻素子处理组可提高大鼠MWT,呈剂量和时间依赖性,并增加大鼠脊髓AP水平。结论钩吻素子具有改善STZ所致DNP的作用,该作用可能与其上调脊髓AP水平有关。Objective To investigate the analgesic effect of koumine on streptozocin(STZ)-induced diabetic neuropathic pain(DNP)model rats,and explore its potential mechanism with the levels of spinal allopregnanolone(AP).Methods According to the mechanical withdrawal threshold(MWT),48 SD rats were randomly assigned into control group(n=6)and STZ treated group(n=42).Rats with successfully induced DNP model were randomly divided into five groups:the model group,the koumine treated group(0.28,1.4 and 7.0 mg/kg)and the gabapentin group(100 mg/kg).The corresponding drug or vehicle was given by intragastric administration from day 22 after STZ administration,once a day for 8 consecutive days.The MWT and body weight of rats were measured to observe the effects of koumine.At the end of the behavioral test,the level of spinal AP was detected by ELISA.Results Koumine had no effect on body weight of DNP rats(P>0.05).Continuous administration of koumine can significantly reverse the mechanical hyperalgesia of DNP rats,and the effect was dose-dependent and time-dependent.Compared with the model group,koumine dose-dependently increased the spinal AP levels in STZ-induced DNP rats.Conclusion Koumine shows significant anti-DNP effect,and its mechanism may be related to the increase of spinal AP levels.

关 键 词：钩吻素子 糖尿病性神经病理性疼痛 链脲佐菌素 脊髓 别孕烯醇酮 大鼠 

分 类 号：R285.5[医药卫生—中药学]