Reg-Ⅲβ和C-fosmRNA在尼莫地平抗大鼠背根反射介导的神经病理痛中的作用  

Reg-Ⅲβ and C-fos mRNA in the inhibitory effects of nimodipine on dorsal root reflexmediated neuropathic pain

作　　者：冯文龙[1,2] 伍磊[1] 林洪[1] 王欢欢[2] 李招胜[1] 陈智彪[1] 沙漠[1] 丁真奇[1] 

机构地区：[1]中国人民解放军第175医院骨科,漳州363000 [2]福建医科大学

出　　处：《临床神经外科杂志》2014年第2期99-102,109,共5页Journal of Clinical Neurosurgery

基　　金：国家自然科学基金81371951(H0605)

摘　　要：目的研究C-fos及Reg-Ⅲβ在大鼠背根反射介导的神经病理痛中的表达变化;并探讨尼莫地平治疗对其的影响。方法建立SD大鼠选择性坐骨神经损伤(SNI)模型,采用Von Frey纤维丝测量不同时间点手术侧后肢的机械痛阈。采用实时荧光定量聚合酶链式反应(RT-qPCR)检测坐骨神经损伤后不同时间内Reg-Ⅲβ及C-fos的mRNA表达,以及不同剂量尼莫地平治疗对这些分子表达的影响。结果与-1 d相比,1、3、5、7、14 d大鼠其SNI术后各时间段脊髓背角组织中的Reg-Ⅲβ及C-fos mRNA表达均普遍上调。腹腔注射尼莫地平对Reg-ⅢβmRNA的表达上调产生明显的时间和剂量依赖性的抑制作用。模型组大鼠的机械痛阈在SNI术后1 d即明显低于基础痛阈,术后5 d降至最低,随后缓慢恢复。尼莫地平治疗后大鼠机械痛阈仍呈下降趋势,但其幅度较模型组显著减小,且术后转归时间显著提前。这些治疗效果随药物浓度提升而明显加大。结论选择性坐骨神经损伤可引起大鼠脊髓背角组织中C-fos及Reg-ⅢβmRNA表达发生时序性变化,尼莫地平能显著减轻神经病理性痛并缩短疼痛转归时间,其机制可能与逆转背根神经节介导的脊髓背角中C-fos及Reg-Ⅲβ的病理性表达有关。Objective To explore the expressions of C-fos and Reg-Ⅲβin the dorsal root of rats with neuropathic pain mediated by dorsal root reflex , and to investigate the effect of nimodipine treatment on them .Methods After the establishment of dorsal root reflex-mediated neuropathic pain by selective spared nerve injury （ SNI） in SD rats, Von Frey filament measurement and real-time fluorescence quantitative polymerase chain reaction （ RT-qPCR ） were performed to determine the mechanical pain threshold of rats ’ hind limbs and the endogenous mRNA expressions of C-fos and Reg-Ⅲβin the dorsal root at different time points , respectively .Nimodipine was given at gradient doses in the experimental rats to examine its effect on the molecular expressions .Results Compared with the unchanged mRNA expressions of C-fos and Reg-Ⅲβin rats from shamed-surgery group , they uniformly increased in rats from SNI groups .After intraperitoneal injection of nimodipine , the increasing tendencies of both C-fos and Reg-Ⅲβexpression were substantially inhibited in a time-and dose-dependent manner .Similar antagonistic effect of nimodipine treatment with regard to mechanical pain threshold was also determined in a dose-dependent manner , which progressively decreased in the SNI model rats as early as 1 day after .surgery compared to the basal level .It continued till 5 days after surgery and followed by a slow recovery .On day 5 after surgery , nimodipine treatment resulted in a significant inhibition on the decline of pain threshold .Conclusions Selective SNI substantially induces mRNA expressions of C-fos and Reg-Ⅲβin the dorsal root of rats .Nimodipine treatment can significantly alleviate the neuropathic pain and reduce its duration , which may be potentially related to the reversal of C-fos and Reg-Ⅲβexpressions .

关 键 词：选择性坐骨神经损伤 Reg-HI B C-FOS 神经病理痛 RT-QPCR 

分 类 号：R730.264[医药卫生—肿瘤]