正清风痛宁对偏头痛大鼠脑干IL-1β、TNF-α表达的影响

Effects of ZhengQing FengTongNing on IL-1β and TNF- α in the brain stem of the rat migraine model

目的观察正清风痛宁对炎性细胞因子白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)在偏头痛大鼠脑干表达的影响。方法将60只Wistar大鼠(雌雄各半)随机分为空白对照组(空白组)、偏头痛模型组(模型组)、舒马普坦组及正清风痛宁高、中、低剂量干预组(高、中、低剂量组)共6组。除空白组外,其余5组大鼠均建立三酰甘油偏头痛模型,用免疫组化SP法测定各组大鼠脑干IL-1β、TNF-α阳性细胞数。结果 6组大鼠间IL-1β、TNF-α阳性细胞数比较差异有统计学意义(分别F=7.063,P=0.001;F=8.257,P=0.000);组间两两比较,模型组脑干IL-1β(18.9±8.17)、TNF-α(14.30±6.41)阳性细胞数较空白组(5.90±2.69、5.00±1.63)增多(分别t=-4.780、P=0.000,t=-4.444,P=0.000),舒马普坦组(2.80±2.15,t=6.026,P=0.000;0.00±0.00,t=7.052,P=0.000)、中剂量组(7.70±4.76,t=3.745,P=0.000;6.20±1.99,t=3.815,P=0.000)、高剂量组(7.80±5.90,t=3.482,P=0.003;5.90±2.88,t=3.778,P=0.001)IL-1β、TNF-α阳性细胞数均较模型组减少;低剂量组脑干IL-1β(13.5±4.30,t=1.849,P=0.081)、TNF-α(11.30±6.11,t=1.071,P=0.298)阳性细胞数与模型组比较差异均无统计学意义;与舒马普坦组比较,低剂量组(t=-7.037,P=0.000;t=-5.847,P=0.000)、中剂量组(t=-2.966,P=0.011;t=-9.858,P=0.000)、高剂量组(t=-2.517,P=0.022;t=-6.467,P=0.000)脑干IL-1β、TNF-α阳性细胞数均增多;与低剂量组比较,中(t=-2.858,P=0.011;t=-2.510,P=0.022)、高剂量组(t=-2.468,P=0.024;t=-2.527,P=0.021)脑干IL-1β、TNF-α阳性细胞数减少;中、高剂量组脑干IL-1β、TNF-α阳性细胞数差异无统计学意义(t=0.042,P=0.967;t=-0.271,P=0.790)。结论正清风痛宁可能抑制偏头痛大鼠炎性细胞因子IL-1β、TNF-α的表达。

Objective To observe the effect of ZhengQing FengTongNing on the expression of inflammatory cytokines IL-1βand TNF-αin the brainstem of migraine rats,discuss the pharmacology of ZhengQing FengTongNing in migraine,and provide the theoretical basis for the development of new drugs for migraine.Methods Sixty Wistar rats（half female and half male）were randomly divided into 6groups：the normal control group,the migraine model group,the sumatriptan group,the ZhengQing FengTongNing lowdose intervention group,the ZhengQing FengTongNing medium-dose intervention group,the ZhengQing FengTongNing high-dose intervention group.Except the normal control group,migraine model of the other 5groups of rats were produced by subcutaneous injection of nitroglycerin.After modeling and drugs intervention,the changes of behavior and symptom of rats were observed,and the number of cells positive for IL-1βand TNF-αin the brainstem of each group were measured by immunohistochemical SP method.Results There were significant differences of the number of cells positive for IL-1βand TNF-αin all the groups（F=7.063,8.257,P 〈0.05）.Further pairwise comparison showed that cells positive for IL-1β（18.9±8.17,t=-4.780,P=0.000）and TNF-α（14.30±6.41,t=-4.444,P=0.000）of the model group were more than the normal control group respectively（P 〈0.05）.Compared with the model group,the number of cells positive for IL-1βand TNF-αin the sumatriptan group（2.80±2.15,t=6.026;0.00±0.00,t=7.052）,the medium-dose group（7.70±4.76,t=3.745;6.20±1.99,t=3.815）and the high-dose group（7.80±5.90,t=3.482,P=0.003;5.90±2.88,t=3.778,P=0.001）were significantly decreased.In the low-dose intervention groups,the number of cells positive for IL-1β（13.5±4.30,t=1.849,P=0.081）and TNF-α（11.30±6.11,t=1.071,P=0.298）in brainstem had no statistical difference compared with the model group.The number of cells positive for IL-1βand TNF-αin brainstem of the sumatriptan group was less than the low-dose intervention group（t=-7.037,P=0.000;t=-5.847,P=0.000）,the medium-dose group（t=-2.966,P=0.011;t=-9.858,P=0.000）,and the high-dose group（t=-2.517,P=0.022;t=-6.467,P=0.000）.Compared with the ZhengQing FengTongNing low-dose intervention group,the number of cells positive for IL-1βand TNF-αsignificantly decreased in brainstem of the medium-dose group（t=-2.858,P=0.011;t=-2.510,P=0.022）and high-dose group（t=-2.468,P=0.024;t=-2.527,P=0.021）;the number of cells positive for IL-1βand TNF-αin the medium-dose group and high-dose group had no statistical difference（t=0.042,P=0.967;t=-0.271,P=0.790）.Conclusions ZhengQing FengTongNing may achieve the effect of treatment in migraine rats,and one of its mechanisms may be inhibiting the expression of inflammatory cytokines IL-1βand TNF-α.