目的观察氟桂利嗪对大鼠偏头痛模型三叉神经节内核苷酸结合寡聚化结构域样受体3(NALP3)炎性小体及白细胞介素1β(IL-1β)的影响。方法选择健康成年雄性SD大鼠55只,取20只随机分为4组,每组5只,分别为空白组、致炎剂1d组、致炎剂3d组、致炎剂7d组,采用免疫印迹方法检测IL-1β的表达。取25只随机分为5组,每组5只,分别为预防对照组、0.5mg/kg氟桂利嗪组、1mg/kg氟桂利嗪组、2mg/kg氟桂利嗪组和4mg/kg氟桂利嗪组,采用免疫印迹法检测各组三叉神经节内NALP3炎性小体及IL-1β的表达。预防对照组和2mg/kg氟桂利嗪组(每组5只)采用免疫荧光方法观察三叉神经节内NALP3炎性小体及IL-1β的表达情况。结果与空白组比较,致炎剂1、3、7d组IL-1β表达明显增高(0.606±0,069,0,868±0.077,0.952±0.098vs0.384±0.027,P〈0.01)。与预防对照组比较,2mg/kg氟桂利嗪组、4mg/kg氟桂利嗪组NALP3、胱天蛋白酶1前体、胱天蛋白酶1、IL-1β表达明显降低(P〈0.01)。2mg/kg氟桂利嗪组NALP3、胱天蛋白酶1、IL-1β荧光红斑较预防对照组明显减弱。结论氟桂利嗪抑制三叉神经初级伤害感觉神经元的炎症作用可能是偏头痛预防治疗的重要机制之一。
Objective To study the effect of flunarizine on NALP3 inflammasome and IL-1β in tri geminal ganglion of a rat migraine model. Methods Twenty healthy adult male SD rats were ran domly divided into blank group and 1-,3-,7-day inflammatory groups (5 in each group). IL-1β ex presston m tngemma est IL-1β expression ganglion was detected by Western blot. evel was established. Twenty-five adult A rat migraine model with the highmale SD rats were randomly divided into prevention control group and 0.5 mg/kg,1 mg/kg,2 mg/kg,4 mg/kg flunarizine groups (5 in each group). Expressions of NALP3 inflammasome and IL-1β in trigeminal ganglion of different groups were detected by Western blot. Expressions of NALP3 inflammasome and IL-1β in trigeminal ganglion of prevention control group and 2 mg/kg flunarizine group were detected by immu- nofluorescence. Results The IL-1βexpression level was significantly higher in 1-, 3-, 7-day inflammatory groups than in blank group (P〈 0. 01). The expression levels of NALP3, procaspase-1, caspase-1 and IL-1β were significantly lower in 2 mg/kg and 4 mg/kg flunarizine groups than in prevention control group (P〈0.01). The fluorescence intensity of NALP3,caspase-1 and IL-1β was significantly lower in 2 mg/kg flunarizine group than in prevention control group. Conclusion Flunarizine role in inhibiting inflammation of trigeminal primary sensory neurons may be one of the important mechanisms for the prevention of migraine.