颅痛颗粒对偏头痛模型大鼠行为学及NF-κB信号转导通路的影响

Effects of Lutong Granules on Behaviors and NF-κB Signal Transduction Pathway in Migraine Rats

【目的】观察颅痛颗粒(袪风药合虫类药)对偏头痛模型大鼠行为学及核因子κB(NF-κB)信号通路的影响,探讨其作用机制。【方法】将60只雄性大鼠随机分为正常组,模型组,西药组,中药高、中、低剂量组,每组10只。中药高、中、低剂量组大鼠分别给予颅痛颗粒(剂量为4.0、2.0、1.0 g·kg-1·d-1)灌胃,西药组给予舒马普坦(剂量为6.0 mg·kg-1·d-1)灌胃,正常组、模型组给予等体积蒸馏水灌胃,连续灌胃7 d后,给予大鼠颈背部皮下一次性注射10 mg/kg硝酸甘油复制偏头痛模型,观察大鼠行为学改变,Western blot法检测脑干NF-κBp65、磷酸化核因子κB抑制蛋白α(p-IκBα)的表达。【结果】(1)行为学变化:与正常组比较,模型组大鼠挠头及爬笼次数均明显增加(P <0.05),于造模后2～5 min出现双耳发红现象;与模型组比较,中药高、中、低剂量组及西药组大鼠挠头及爬笼次数均明显减少,耳红出现时间延后,耳红持续时间缩短(P <0.05),且中药各剂量组的治疗作用呈剂量依赖性。(2)NF-κBp65、p-IκBα的表达:与正常组比较,模型组脑干NF-κBp65、p-IκBα蛋白表达升高;与模型组比较,中药高、中、低剂量组及西药组NF-κBp65、p-IκBα蛋白表达均降低(P <0.05),且中药各剂量组的治疗作用呈剂量依赖性。【结论】颅痛颗粒可改善偏头痛大鼠的行为学变化,其作用机制可能与抑制脑干NF-κB信号通路的激活有关。

Objective To observe the effects of Lutong Granules(mainly composed of wind-dispelling drug and worm drug)on behaviors and nuclear factor kappa B(NF-κB)signal transduction pathway in migraine rats,so as to explore its mechanisms.Methods Sixty male rats were randomly divided into normal group,model group,western medicine group,and high-,middle-and low-dose Chinese medicine groups,10 rats in each group.The high-,middle-and low-dose Chinese medicine groups were given intragastric administration of Lutong Granules(at the dosage of 4.0,2.0,1.0 g·kg-1·d-1),the western medicine group was given intragastric administration of Sumatriptan(at the dosage of 6.0 mg·kg-1·d-1),the normal group and model group were given intragastric administration of the same volume of distilled water,and after medication for 7 continuous days,the migraine rat model was established by one-time subcutaneous injection of 10 mg/kg of nitroglycerin into the napex.And then we observed the rat behaviors,and detected the protein expression levels of brainstem NF-κBp65 and phosphorylated inhibitor of kappa B alpha(p-IκBα)by Western blot method.Results(1)Behavioral changes:compared with the normal group,the frequency of rat scratching head and climbing the cage was increased,and the auricular congestion appeared 2-5 minutes after modeling in the model group(P<0.05);compared with the model group,the frequency of rat scratching head and climbing the cage was decreased,the time for auricular congestion appearance was prolonged and the time for auricular congestion disappearance was shortened in the high-,middle-and low-dose Chinese medicine groups and western medicine group(P<0.05),the effects in various Chinese medicine groups being dose-dependent.(2)Expression of NF-κB and p-IκBα:compared with the normal group,the protein expression levels of NF-κB and p-IκBαwere increased in the model group(P<0.05);compared with the model group,the protein expression levels of NF-κB and p-IκBαwere decreased in the high-,middle-and low-dose Chinese medicine groups and western medicine group(P<0.05),the effect invarious Chinese medicine groups being dose-dependent.Conclusion Lutong Granules can improve the behavioral changes of migraine rats,and the therapeutic mechanism was related to inhibiting the activation of NF-κB signal pathway in the brainstem of migraine rats.