摘要
目的探讨辛伐他汀(SVT)对白蛋白结合型紫杉醇导致的神经病理性疼痛的作用及其机制。方法54只雄性SD大鼠被随机分为紫杉醇组、紫杉醇+SVT组和对照组,每组18只。紫杉醇组和紫杉醇+SVT组实验第1,3,5,7天腹腔注射白蛋白结合型紫杉醇(2.47 mg/kg)建立神经病理性疼痛模型,大鼠出现机械痛敏和热痛敏为造模成功。紫杉醇+SVT组在造模同时,第1~7天每日腹腔注射辛伐他汀(15 mg/kg);对照组给予等量生理盐水腹腔注射。实验第4,8天检测各组大鼠的机械刺激缩足反射阈值(MWT)和热刺激缩足反射潜伏期(TWL);实验第8天取大鼠L4-6脊髓。免疫组化及免疫荧光法检测L4-6脊髓组织中胶质纤维酸性蛋白(GFAP)及离子钙接头蛋白抗体-1(Iba-1)的表达、caveolin-1/Toll样受体4(TLR4)通路中caveolin-1和TLR4的表达,Western blot检测微管相关蛋白-2(MAP-2)、MAP-4、MAP-6的表达,ELISA检测TNF-α、IL-1β和IL-6的水平。结果与对照组相比,紫杉醇组MWT、TWL均降低(P<0.05),提示神经病理性疼痛模型成功建立;与紫杉醇组相比,紫杉醇+SVT组MWT、TWL均升高(P<0.05)。紫杉醇组大鼠L4-6脊髓组织中caveolin-1、TLR4、GFAP、Iba-1、MAP-2、MAP-4、MAP-6、TNF-α、IL-1β和IL-6的表达水平均高于对照组(均P<0.05),而紫杉醇+SVT组各指标低于紫杉醇组(均P<0.05)。结论辛伐他汀可通过抑制caveolin-1/TLR4通路降低炎性因子TNF-α、IL-1β和IL-6的表达水平,减少微管相关蛋白MAP-2、MAP-4、MAP-6的表达,进而缓解白蛋白结合型紫杉醇导致的神经病理性疼痛。
Objective To investigate the effect and mechanism of simvastatin on neuropathic pain induced by nab-paclitaxel.Methods Fifty-four male SD rats were randomly divided into three groups:control group,paclitaxel group and paclitaxel+simvastatin(SVT)group,with 18 rats in each group.The neuropathic pain model was established by intraperitoneal injection of nab-paclitaxel(2.47 mg/kg)at days 1,3,5,7 with a final cumulative dose of 9.9 mg/kg in paclitaxel group and paclitaxel+SVT group.The neuropathic pain model was successfully established when rats developed mechanical hyperalgesia and thermal hyperalgesia.Rats were intraperitoneally injected with nab-paclitaxel and SVT(15 mg/kg,7 consecutive days)in paclitaxel+SVT group,and rats in control group were given an equal dose of normal saline.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)of rats in each group were detected at day 4 and day 8.At day 8,the L4-6 spinal cord of rats was collected.Immunohistochemistry and immunofluorescence staining were used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium binding adaptor molecule-1(Iba-1),caveolin-1 and toll like receptor 4(TLR4)protein in caveolin-1/TLR4 pathway.Western blot was used to detect the expression of microtubule-associated proteins MAP-2,MAP-4 and MAP-6.ELISA was used to detect the levels of inflammatory factors tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6).Results Compared with control group,MWT and TWL in paclitaxel group were decreased(P<0.05);compared to paclitaxel group,MWT and TWL were increased in paclitaxel+SVT group(P<0.05).The expression levels of caveolin-1,TLR4,GFAP,Iba-1,MAP-2,MAP-4,MAP-6,TNF-α,IL-1βand IL-6 in the L4-6 spinal cord tissue in paclitaxel group were higher than those in control group(all P<0.05).These above indicators were lower in paclitaxel+SVT group than those in paclitaxel group(all P<0.05).Conclusion Simvastatin can alleviate the neuropathic pain caused by nab-paclitaxel by reducing the expres
作者
魏星
马莉
王力
王颖
李维妙
周雅卿
赵永林
WEI Xing;MA Li;WANG Li;WANG Ying;LI Weimiao;ZHOU Yaqing;ZHAO Yonglin(Department of Gynaecology and Obstetrics,Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Department of Oncology,Second Affiliated Hospital of Xi’an Jiaotong University)
出处
《山西医科大学学报》
CAS
2022年第8期1004-1010,共7页
Journal of Shanxi Medical University
基金
国家自然科学基金资助项目(82001327)。
