5-HT_1受体激动剂对偏头痛大鼠脑膜神经源炎症的影响

The Role of 5-HT_1 Receptors Agonists in Neurogenic Inflammation of Dura Maters of Intravenous Glyceryl Trini-trate-induced Rats

目的探讨5-HT_1受体激动剂94-95-10Y及二氢麦角胺(DHE)对偏头痛大鼠神经源性脑膜炎症的作用与机制。方法采用静脉注射硝酸甘油(GTN)制备大鼠偏头痛模型;94-95-10Y10、20、30mg/kg组在制作模型前20min腹腔注射94-95-10Y10、20、30mg/kg,DHE组在GTN静脉注射15min时静脉注射DHE;在GTN静脉注射后2h、4h,分别取脑膜组织,Western印迹法检测脑膜核因子-kB(NF-kB)、细胞间黏附分子-1(ICAM-1)蛋白表达水平,部分脑膜制成组织切片,观察脑膜病理变化。结果94-95-10Y10、20、30mg/kg组及DHE组大鼠脑膜炎性细胞明显减少,血管扩张程度减轻;94-95-10Y10、20、30mg/kg组及DHE组均能抑制GTN静脉注射大鼠脑膜NF-kB、I- CAM-1蛋白表达,94-95-10Y10、20、30mg/kg各组呈剂量依赖关系。结论94-95-10Y及DHE能够抑制偏头痛大鼠脑膜NF-kB、ICAM-1蛋白表达增强及脑膜炎症反应,提示5-HT_1受体激动剂可以阻断NF-kB信号通路发挥其抗偏头痛时神经源性脑膜炎症的作用。

Objective To understand the role and mechanism of 5-HT1 receptors agonists,compound 94-95-10Y and DHE in neurogenic inflammation of dura maters in migraine rats. Methods Rat migraine model was obtained with GTN infusion. 94-95-10Y（10,20,30mg/kg） and DHE were administered 20min before GTN infusion and 15min after GTN infusion,respectively. NF-κB and ICAM-1 protein expressions in rat dura maters were examined 2h and 4h after normal saline or GTN infusion by western-blot,respectively. Meanwhile ,we examined the inflammatory response in rat dura maters 2h after normal saline or GTN infusion by histochemistry. Results 94-95-10Y and DHT alleviated the inflammatory response and blood vascular dilatation in dura maters of GTN infusion rats. After administration of 94-95-10Y （10,20,30mg/kg） and DHE ,NF-κB and ICAM-1 protein expression levels of dura maters of GTN infusion rats were reduced. Conclusion 94-95-10Y and DHE inhibits the increases of NF-κB and ICAM-1 protein expression levels in dura maters of migraine rats. It also alleviates the inflammatory response in dura maters of migraine rats. As a concluding remark,5-HT1 receptors agonists might be anti-migraine drug and their effects lie in inhibiting neurogenic inflammation of dura maters by the blockade of NF-κB signal pathway.