背根神经节ZHX2在外周神经损伤痛觉过敏中的作用研究  

Effect of zinc-fingers and homeoboxes 2 in the dorsal root ganglion on peripheral nerve injuryinduced pain hypersensitivity

作　　者：龚华磊[1] 徐华丽[2] 磨凯[2] Gong Hualei;Xu Huali;Mo Kai(Department of Organ Transplantation,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China;Department of Anesthesiology,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China)

机构地区：[1]南方医科大学珠江医院器官移植科,广州510282 [2]南方医科大学珠江医院麻醉科,广州510282

出　　处：《中华神经医学杂志》2018年第9期918-924,共7页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金（2017A030313599）南方医科大学青年科技人员培育项目（PY2016N014）

摘　　要：目的探讨背根神经节（DRG）锌指和同源框蛋白家族（ZHX）在外周神经损伤痛觉过敏中的作用，为神经病理性疼痛（NP）的分子生物学机制提供新的思路。方法（1）24只8周龄雄性C57BL6小鼠，按随机数字表法分为坐骨神经慢性缩窄性损伤模型（CCI）组、假手术组，每组12只，造模前1d、造模后7d检测小鼠机械缩爪反应频率（PwF）和热缩爪反应潜伏期（PWL）的变化。造模后7d采用反转录实时定量PCR（RT-qPCR）检测小鼠DRGZHX1、ZHX2、ZHX3mRNA的表达；采用Westernblotting检测小鼠DRGZHX2蛋白的表达。（2）36只8周龄雄性C57BL6小鼠，按随机数字表法分为DRG内注射等剂量溶剂、无义阴性对照序列（siNC）、ZHX2小f扰RNA（siRNA）的CCI组和DRG内注射等剂量溶剂、siNC、ZHX2siRNA的假手术组．每组6只。注射药物前1d、注射药物后7d观察6组小鼠机械缩爪反应频率（PWF）和热缩爪反应潜伏期（PWL）的变化：RT-qPCR检测小鼠DRGZHX2mRNA的表达。结果（1）造模后7d，与假手术组患侧比较，CCI组小鼠患侧后爪PWF明显增加、PWL明显缩短，差异均有统计学意义（P〈0．05）：与假手术组比较，CCI组小鼠DRGZHX2mRNA的表达增加1．71倍，差异有统计学意义（P〈0．05）；与假手术组患侧比较，CCI组小鼠患侧DRGZHX2蛋白的表达增加2．15倍，差异有统计学意义（P〈0．05）；（2）与注射溶剂、siNC、siRNA的假手术组比较，注射溶剂、sinC的CCI组小鼠患侧PWF增加、PWL降低、DRGZHX2mRNA的表达增加，差异均有统计学意义（P〈0．05）。与注射溶剂、siNC的CCI组比较，注射siRNA的CCI组小鼠患侧PWF降低、PWL增加、DRGZHX2mRNA的表达降低，差异均有统计学意义（P〈0．05）。结论外周神经损伤上调受损DRG内ZHX2的表达，抑制ZHX2高表达可缓解神经损伤引起的痛觉过敏行为。Objective To explore the roles of zinc-fingers and homeoboxes （ZHX） in the dorsal root ganglia （DRG） in peripheral nerve injury-induced pain hypersensitivity, and provide a new idea for molecular mechanism ofneuropathic pain （NP）. Methods （1） Twenty-four 8-week-old male C57BL6 mice were randomly divided into sham-operated group and chronic constriction injury （CCI） of the sciatic nerve model group （n=12）. One d before modeling and 7d after modeling, the changes of paw withdrawal frequency （PWF） to mechanical stimuli and paw withdrawal latency （PWL） to thermal stimulation were detected. Seven d after modeling, reverse transcription real-time quantitative PCR （RT-qPCR） was used to detect the ZHX1, ZHX2, and ZHX3 mRNA expressions, and Western blotting was employed to detect the ZHX2 protein expression. （2） Thirty-six 8-week-old male C57BL6 mice wererandomly divided into equivalent dose solvent CCI group, nonsense negative control sequence [siNC] CCI group and ZHX2 siRNA CCI group, and equivalent dose solvent sham-operated group, siNC sham-operated group and ZHX2 siRNA sham-operated group （n=6）; each treatment was given to the DRG. One d before drug injection and 7 d after drug injection, the changes of PWF to mechanical stimuli and PWL to thermal stimulation were detected; RT-qPCR was used to detect the ZHX2 mRNA expression. Results （1） Seven d after modeling, PWF was significantly increased and PWL was statistically shorten in the hind-paw of the ipsilateral side in the CCI group as compared with those in the sham-operated group （P〈0.05）; DRG ZHX2 mRNA expression in the CCI group increased for 1.71 times as compared with that in the sham-operated group, with significant difference （P〈0.05）; DRG ZHX2 protein expression in the CCI group increased for 2.15 times as compared with that in the sham-operated group, with significant difference （P〈0.05）. （2） As compared with the equivalent dose solvent sham-operated group, siNC sham-operated group and ZHX

关 键 词：背根神经节 锌指和同源框蛋白2 神经损伤 神经病理性疼痛 

分 类 号：R363.2[医药卫生—病理学]