纹状体HCN4通道在紫杉醇诱发大鼠神经病理性痛中的作用:与GABAB受体的关系  

Role of striatal HCN4 channels in striatum in paclitaxel-induced neuropathic pain in rats:its relationship with GABAB receptors

作　　者：缑泽鹏 田晓琳 于伟凡 赵爽[1] 刘朋[1] 李惠洲 刘欣[1] 王秀丽[1] Gou Zepeng;Tian Xiaolin;Yu Weifan;Zhao Shuang;Liu Peng;Li Huizhou;Liu Xin;Wang Xiuli(Department of Anesthesiology,Third Hospital of Hebei Medical University,Shijiazhang 050051,China)

机构地区：[1]河北医科大学第三医院麻醉科,石家庄050051

出　　处：《中华麻醉学杂志》2020年第7期859-862,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81971001);河北省自然科学基金课题(H2018206260)。

摘　　要：目的评价纹状体超极化激活环核苷酸门控通道(HCN通道)在紫杉醇诱发大鼠神经病理性痛中的作用及其与GABAB受体的关系。方法清洁级健康雄性SD大鼠,6~9周龄,体重180~220 g。腹腔注射紫杉醇2 mg/kg,每2 d注射1次,连续7 d,制备神经病理性痛模型,随后行鞘内置管术。选取鞘内置管术成功的大鼠50只,采用随机数字表法分为5组(n=10):紫杉醇组(P组)、紫杉醇+生理盐水组(N组)、紫杉醇+慢病毒空载体组(BV组)、紫杉醇+HCN4通道慢病毒组(H组)和紫杉醇+HCN通道阻断剂ZD7288组(I组)。选取10只同龄大鼠作为空白对照组(C组)。腹腔注射紫杉醇后15 d时,N组鞘内注射生理盐水20μl,BV组鞘内注射HCN4通道慢病毒空载体1×10^8 TU/ml(20μl),H组鞘内注射HCN4通道慢病毒1×10^8 TU/ml(20μl),I组鞘内注射ZD728830μg(20μl)。腹腔注射紫杉醇前1 d和注射后14、21 d时测定机械缩足反应阈(MWT)。于T2时取大脑纹状体组织,采用免疫组织化学法和Western blot法测定HCN4通道和GABAB受体表达水平。结果与C组比较,P组MWT降低,HCN4通道表达上调,GABAB受体表达下调(P<0.05);与P组比较,H组和I组MWT升高,HCN4通道表达下调,GABAB受体表达上调(P<0.05),N组和BV组上述指标差异无统计学意义(P>0.05)。结论纹状体HCN4通道表达上调可诱导GABAB受体表达下调,参与紫杉醇诱发大鼠神经病理性痛的病理生理机制。Objective To evaluate the role of hyperpolarization-activated cyclic nucleotide-gated(HCN)channels in striatum in paclitaxel-induced neuropathic pain and the relationship with GABAB receptors in rats.Methods Healthy clean-grade male Sprague-Dawley rats,aged 6-9 weeks,weighing 180-220 g,were used in this study.The neuropathic pain model was established by intraperitoneal injection of paclitaxel 2 mg/kg once every 2 days for 7 consecutive days in anesthetized rats,and then intrathecal catheterization was performed.Fifty rats in which intrathecal catheters were successfully implanted were divided into 5 groups(n=10 each)using a random number table method:paclitaxel group(P group),paclitaxel plus normal saline group(N group),paclitaxel plus lentivirus empty vector group(BV group),paclitaxel plus HCN4 channel lentivirus group(H group),and paclitaxel plus HCN channel inhibitor ZD7288 group(I group).Ten rats of the same age were selected as the blank control group(C group).At 15 days after intraperitoneal injection of paclitaxel,normal saline 20μl was intrathecally injected in group N,group BV received intrathecal injection of HCN4 channel lentivirus empty vector 1×10^8 TU/ml,20μl,group H received intrathecal injection of HCN4 channel lentivirus 1×10^8 TU/ml,20μl,and group I received intrathecal injection of ZD728830μg,20μl.The mechanical paw withdrawal threshold(MWT)was measured at 1 day before paclitaxel injection and 14 and 21 days after injection.The cerebral striatum tissues were obtained at T2,and the expression of HCN4 channel and GABAB receptors was determined by immunohistochemistry and Western blot.Results Compared with group C,the MWT was significantly decreased,HCN4 channel expression was up-regulated,and GABAB receptor expression was down-regulated in group P(P<0.05).Compared with group P,the MWT was significantly increased,HCN4 channel expression was down-regulated,and GABAB receptor expression was up-regulated in group H and group I(P<0.05),and no significant change was found in the parameters ment

关 键 词：白蛋白结合型紫杉醇 神经痛 超极化-活化环核苷酸-门控通道 受体 GABA-B 纹状体 

分 类 号：R730.53[医药卫生—肿瘤] R741.041[医药卫生—临床医学]