神经调节蛋白/表皮生长因子受体通路在偏头痛大鼠模型中的作用

目的 探讨神经调节蛋白(neuregulin,NRG)/表皮生长因子受体(epidermal growth factor receptor,ErbB)通路在偏头痛大鼠模型中的作用。方法 将Wistar大鼠随机分为对照组、模型组、空载(空慢病毒载体)组、NRG沉默(含NRG基因干扰片段的慢病毒载体)组、NRG1(0.01 mg/kg)组,每组各12只; 除对照组外,其余各组制备偏头痛大鼠模型,观察大鼠行为学表现,记录一段时间内大鼠挠头次数、爬笼次数; 测定各组大鼠机械性刺激及温度痛阈; 用酶联免疫吸附实验(Enzyme linked immunosorbent assay,ELISA)检测各组大鼠血清肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α),白介素-6(Interleukin-6,IL-6)水平; 免疫印迹实验检测各组大鼠脑组织NRG/ErbB通路相关蛋白表达水平。结果 与对照组比较,模型组、空载组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平明显增高,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白NRG表达水平及ErbB/磷酸化表皮生长因子受体(phospho-epidermal growth factor receptor,p-ErbB)明显降低(P<0.05)。与模型组比较,空载组大鼠各指标水平无明显变化(P>0.05); NRG沉默组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平增高,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白NRG表达水平及ErbB/p-ErbB降低(P<0.05); NRG1组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平降低,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白ErbB/p-ErbB增高(P<0.05),NRG表达水平无明显变化(P>0.05)。结论 NRG/ErbB通路可调控大鼠偏头痛,上调该通路可减轻其头痛。

The role of NRG/ErbB pathway in migraine rat models

ObjectiveTo investigate the role of NRG/ErbB pathway in migraine rat models.Methods Wistar rats were randomly divided into control group, model group, no-load(empty lentivirus vector)group, NRG silencing(lentivirus vector containing NRG gene interference fragment)group and NRG1(0.01 mg/kg)group, with 12 rats in each group. Migraine rat models were prepared in all groups except control group, the behavior manifestations of rats was observed, and the number of head scratching, number of cage climbing were recorded, the mechanical stimulation and temperature pain threshold were measured, the serum TNF-α and IL-6 levels were measured by ELISA, and the NRG/ErbB pathway-related protein expressive levels in brain tissue of rats in each group was detected by Western blotting.Results Compared with the control group, the number of head scratching, number of cage climbing, serum TNF-α and IL-6 levels in the model group and no-load group increased significantly, while the pain threshold of mechanical stimulation, latency of thermal stimulation, NRG/ErbB pathway-related protein NRG expressive level and ErbB/p-ErbB in brain tissue decreased significantly(P<0.05). Compared with the model group, there was no significant change in each index in the no-load group(P>0.05), in NRG silencing group the number of head scratching, number of cage climbing, serum TNF-α and IL-6 levels increased, while the pain threshold of mechanical stimulation, latency of thermal stimulation, NRG/ErbB pathway-related protein NRG expressive level and ErbB/p-ErbB in brain tissue decreased, in NRG1 group the number of head scratching, number of cage climbing, serum TNF-α and IL-6 levels decreased, and the pain threshold of mechanical stimulation, latency of thermal stimulation, NRG/ErbB pathway-related protein expressive level and ErbB/p-ErbB in brain tissue increased, while the NRG expressive level did not change significantly(P>0.05).Conclusion NRG/ErbB pathway could regulate migraine in rats, and up-regulation of NRG/ErbB pathway could decrease headache.