钩吻素子对大鼠神经病理性痛行为学和脊髓机制研究  

Analgesic Effect of Koumine on Neuropathic Pain and its Mechanism in Spinal Cord of Rats

作　　者：金桂林[1] 何赛娣 岳荣彩 许盈[1] 叶丽香[2] 俞昌喜[1] JIN Guilin;HE Saidi;YUE Rongcai;XU Ying;YE Lixiang;YU Changxi(College of Pharmacy,Fujian Medical University,Fuzhou 350122,China;Fujian Center for Safety Evaluation of New Drug,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学药学院药理学系,福州350122 [2]福建医科大学福建省新药安全性评价中心,福州350122

出　　处：《福建医科大学学报》2019年第4期209-213,共5页Journal of Fujian Medical University

基　　金：福建省自然科学基金(2016J05191;2018J01815)

摘　　要：目的观察钩吻素子对大鼠坐骨神经分支选择性损伤(SNI)的痛行为作用,并探讨其对脊髓自噬和星型胶质细胞活化的相关机制。方法将SNI及假手术大鼠随机分为5组,分别为假手术组、模型组、钩吻素子高剂量组(3 mg/kg)、钩吻素子低剂量组(0.6 mg/kg)和加巴喷丁对照组(加巴喷丁,800 mg/kg)。术后第3天通过灌胃给予相应药物,每日2次,连用7 d。以大鼠机械痛阈值为指标,观测钩吻素子对SNI诱导神经病理性疼痛(NP)大鼠的镇痛作用。行为学实验结束后,各组大鼠经灌注固定后取脊髓,采用Western-blot法检测胶质纤维酸性蛋白和自噬相关蛋白LC3,Beclin 1及p62的表达水平。结果与SNI模型组比较,钩吻素子高剂量组及加巴喷丁对照组大鼠的机械痛阈值显著增高。钩吻素子显著降低SNI大鼠脊髓的胶质纤维酸性蛋白(GFAP)水平,并显著增强LC3和p62的表达,对Beclin 1无显著影响。结论钩吻素子具有显著的抗SNI大鼠机械刺激诱发痛的作用,其作用机制可能与降低脊髓星形胶质细胞活化水平及上调自噬水平有关。Objective To observe the effect of koumine on spared nerve injury(SNI)induced neuropathic pain(NP)and its possible mechanism with autophagy and astrocyte activation.MethodsSNI rats and sham SNI rats were randomly assigned into five groups:the sham operation group,the SNI group,the koumine treatment groups(0.6 and 3 mg/kg),and the gabapentin control group(800 mg/kg).On postoperative day 3,the drugs or vehicle was administered intragastrically twice a day for 7 consecutive days.The mechanical pain threshold was measured on the day before surgery,on postoperative day 3(predosing),and on 1 h after drug administration(postdosing).At the end of the behavioural experiment,the spinal cord was obtained after perfusion fixation.The level of glial fibrillary acidic protein(GFAP),Beclin-1,LC3-Ⅱ,LC3-Ⅰand p62 were measured by Westernblot.ResultsKoumine(3 mg/kg)and gabapentin had significant improved mechanical threshold of SNI rats.Koumine significantly reduced the GFAP level in the spinal cord of SNI rats.Koumine significantly enhanced the expression of LC3 and p62,but had no significant effect on Beclin 1.ConclusionThese results suggest that the analgesic effect of koumine on SNI induced NP may involve the inhibition of astrocyte activation and promotion autophagy in the spinal cord.

关 键 词：钩吻碱 神经系统/病理性 疼痛 神经胶质 星形细胞 自噬 脊髓 大鼠 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]