[1]盛恒炜,磨凯.ZHX2在调控背根神经节m阿片受体表达致神经病理性痛中的作用[J].南方医科大学学报,2019,(08):917.[doi:10.12122/j.issn.1673-4254.2019.08.07]
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ZHX2在调控背根神经节m阿片受体表达致神经病理性痛中的作用()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年08期
页码:
917
栏目:
出版日期:
2019-08-31

文章信息/Info

Title:
Role of ZHX2 in regulating dorsal root ganglion μ-opioid receptor expression in mice with peripheral nerve injury-induced pain hypersensitivity
作者:
盛恒炜磨凯
关键词:
背根神经节锌指和同源框蛋白2m阿片受体神经损伤神经病理性疼痛
Keywords:
dorsal root ganglia zinc-fingers and homeoboxes 2 μ-opioid receptor nerve injury neuropathic pain
DOI:
10.12122/j.issn.1673-4254.2019.08.07
摘要:
目的探讨背根神经节(DRG)转录因子锌指和同源框蛋白2(ZHX2)在调控外周神经损伤m阿片受体(MOR)表达致痛觉 过敏的作用,为临床治疗神经病理性疼痛(NP)提供实验理论依据。方法取48只8周龄雄性C57BL6J小鼠,按随机数字表法分 为4 组:DRG内分别注射无义阴性对照序列(siNC)、ZHX2 siRNA 的坐骨神经慢性缩窄性损伤模型(CCI 组)和siNC、ZHX2 siRNA的假手术组,每组12只。注射药物后7 d收集DRG组织,RT-qPCR和Western blot分别检测小鼠DRG ZHX2和MOR转 录和翻译的表达及机械痛阈(PWF)改变。取6只21 d龄SPF级健康成年雄性C57BL6J小鼠,提取上述小鼠DRG组织行原代细 胞培养,分为2组(每组3个重复):转染siNC和ZHX2 siRNA组。转染后48 h,收集细胞分别检测ZHX2和MOR转录和翻译的 表达。结果与注射siNC 和siRNA 的假手术组比较,注射对照的siNC CCI 组DRG ZHX2 mRNA和蛋白质表达均增加,而 MOR mRNA和蛋白质表达均下调,差异均有统计学意义(P<0.05)。而与注射siNC的CCI组比较,注射siRNA的CCI组小鼠 DRG ZHX2 mRNA和蛋白质表达下调,同时增加MOR mRNA和蛋白质表达,差异均有统计学意义(P<0.05)。在痛行为上,与 注射siNC 的CCI组比较,注射siRNA的CCI组小鼠患侧PWF降低,差异有统计学意义(P<0.05)。与转染siNC 组比较,转染 ZHX2 siRNA组ZHX2的mRNA和蛋白质表达降低同时促进MOR转录和翻译表达增加,差异均有统计学意义(P< 0.05)。结 论敲减外周神经损伤引起的DRG ZHX2高表达,逆转MOR表达下调,从而缓解神经损伤引起的痛觉过敏行为。
Abstract:
Objective To investigate the role of zinc-fingers and homeoboxes 2 (ZHX2) in regulating μ-opioid receptor expression in the dorsal root ganglion (DRG) in mice with peripheral nerve injury-induced pain hypersensitivity. Methods Forty-eight male adult C57BL6J mice were randomized into 4 groups and subjected to chronic constriction injury (CCI) of the sciatic nerve or sham operation followed by microinjection of a specific small interfering RNA (siRNA) of ZHX2 or a negative control siRNA sequence (siNC) into the DRG. Seven days later, the mice were examined for changes in the hind paw withdrawal frequency (PWF), after which the DRG tissue was collected for detecting the expressions of μ-opioid receptor at the mRNA and protein levels using RT-qPCR and Western blotting. In another experiment, the DRG tissues were collected from 6 mice (21-day-old) for primary culture of the DRG neurons, which were transfected with ZHX2 siRNA or the siNC to observe the changes in the expressions of ZHX2 and μ-pioid receptor. Results Microinjection of ZHX2 siRNA into the ipsilateral L3 and L4 DRGs significantly reversed CCI-induced μ-pioid receptor downregulation in the injured DRG and alleviated CCI-induced mechanical allodynia in the mice. In the cell experiment, ZHX2 knockdown obviously upregulated the mRNA and protein expressions of opioid receptor in the primary cultured DRG neurons. Conclusion ZHX2 knockdown in the DRG reverses CCI-induced down-regulation of μ opioid receptor to alleviate periphery nerve injury-induced pain hypersensitivity in mice.

相似文献/References:

[1]徐华丽,徐世元,磨凯.蛋白精氨酸甲基化酶在小鼠外周神经损伤后背根神经节中的转录表达[J].南方医科大学学报,2017,(12):1620.
[2]赵其宏,王其友,徐杰,等.碘乙酸钠诱导的骨关节炎疼痛大鼠背根神经节KCNA2 的表达[J].南方医科大学学报,2019,(05):579.[doi:10.12122/j.issn.1673-4254.2019.05.13]

更新日期/Last Update: 1900-01-01