文章摘要
周 芳,夏中元,刘 康,黄亚医,周 芹.NRG1对糖尿病大鼠神经病理性疼痛的影响[J].,2019,19(14):2642-2645
NRG1对糖尿病大鼠神经病理性疼痛的影响
Neuregulin 1 Role in Diabetic Neuropathic Pain
投稿时间:2018-12-08  修订日期:2018-12-31
DOI:10.13241/j.cnki.pmb.2019.14.008
中文关键词: NRG1  糖尿病  疼痛  NGF  炎症因子
英文关键词: NRG1  Diabetes Mellitus  Pain  NGF  Inflammatory Cytokines
基金项目:中央高校基本科研业务费专项基金(2042018kf0199)
作者单位E-mail
周 芳 武汉大学人民医院麻醉科 湖北 武汉 430060 zhfang1005@126.com 
夏中元 武汉大学人民医院麻醉科 湖北 武汉 430060  
刘 康 武汉大学人民医院麻醉科 湖北 武汉 430060  
黄亚医 武汉大学人民医院麻醉科 湖北 武汉 430060  
周 芹 武汉大学人民医院麻醉科 湖北 武汉 430060  
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中文摘要:
      摘要 目的:研究外源性神经调节蛋白1(neuregulin-1, NRG1)对糖尿病大鼠神经病理性疼痛的影响及可能的机制。方法:采用腹腔注射60 mg/kg链脲佐菌素(streptozocin,STZ)诱导糖尿病模型,造模成功的大鼠随机分为糖尿病组(D组)及NRG1静脉注射组(N组),另取同月龄大鼠为正常对照组(C组)。造模成功后两周N组大鼠通过尾静脉注射NRG1(10 μg? kg-1?d-1)连续给药1周 ,C组及D组则予以生理盐水对照。每周测定大鼠机械性刺激缩足反应的阈值(Mechanical withdrawal threshold, MWT),诱导七周后采用Western-blotting方法测定脊髓NRG1, NGF, IL-1β 和TNF-α的蛋白表达,并采用透射电镜观察大鼠腓肠神经的超微病理结构。结果:与糖尿病组相比,NRG1干预组的痛阈明显提高,腓肠神经病理学改变明显减轻。糖尿病组脊髓腰膨大NRG1、NGF、 IL-1β 和TNF-α含量分别为(0.337±0.092)、(0.371±0.060)、(0.619±0.089)、(0.752±0.071),与对照组相比均有显著性差异(P<0.05);NRG1组NGF、 IL-1β 和TNF-α表达量分别为(0.576±0.061)、(0.375±0.029)、(0.524±0.056),与糖尿病组相比均有统计学差异(P<0.05)。结论:静脉给予外源性NRG1能够预防和减轻糖尿病大鼠神经病理性疼痛,其机制可能与NRG1刺激NGF的生成及抑制炎性因子的释放有关。
英文摘要:
      ABSTRACT Objective: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group (group C), diabetic group (group D), NRG1 intervention group (group N). 2 weeks after STZ-induced, group N were received 10 μg? kg-1?d-1 rhNRG1 intravenous injection for 7 consecutive days, while group C and D were received vehicle (saline). 4 weeks after NRG1 intervention, the MWT and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, western blotting was used to detect the expression of NGF, IL-1β, TNF-α in spinal cord. Results: Compared with group D, administration of NRG1 significantly attenuated the development of mechanical allodynia in diabetic rats(P<0.05), and the pathological changes of dorsal root ganglion and sural nerve were alleviated. The expression of NRG1, NGF, IL-1β and TNF-α in group D were(0.337±0.092),(0.371±0.060),(0.619±0.089),(0.752±0.071)respectively, and compared with group C, there were statistical differences(P<0.05); The expression of NGF, IL-1β and TNF-α in group N were(0.576±0.061),(0.375±0.029),(0.524±0.056)respectively, and compared with group D, there were statistical differences(P<0.05). Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of STZ-induced diabetic rats, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.
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