PKC ε-ERK1/2信号通路抑制剂对急性偏头痛大鼠模型硬脑膜血流量的影响

Effects of PKCε-ERK1/2 signaling pathway inhibitor on the dural blood flow in a rat model of acute migraine

目的探讨急性偏头痛模型大鼠中应用PKCε-ERK1/2信号通路抑制剂对硬脑膜血流量的影响。方法选择成年雄性SD大鼠60只,按照随机数字表法将其随机分为6组,每组10只。分别为对照组(N组),假手术组(S组),偏头痛模型组(M组),偏头痛模型+二甲基亚砜组(DMSO组),偏头痛模型+PKCε抑制剂组(H-7组)和偏头痛模型+ERK1/2抑制剂组(PD-98059组)。造模后即刻,侧脑室注射给药,利用激光多普勒血流量图像仪记录硬脑膜血流量变化情况,并比较各组造模后2 h硬脑膜血流量变化百分比。结果 S组与N组硬脑膜血流量变化百分比比较,差异无统计学意义(P>0.05);与S组相比,M组、DMSO组硬脑膜血流量变化百分比明显增加[(78.0±4.2)%比(3.8±1.0)%,(76.5±6.2)%比(3.8±1.0)%,P均<0.05];H-7组较M组、S组硬脑膜血流量变化百分比均明显减少[(-24.8±4.9)%比(78.0±4.2),(-24.8±4.9)%比(3.8±1.0)%,P均<0.05];PD-98059组与M组相比,硬脑膜血流量变化百分比明显减少[(29.4±3.9)%比(78.0±4.2)%,P<0.05],但与S组相比,硬脑膜血流量变化百分比明显增加[(29.4±3.9)%比(3.8±1.0)%,P<0.05]。结论大鼠偏头痛发作过程中硬脑膜血流量明显增加,PKCε及ERK1/2抑制剂均可明显降低硬脑膜血流量。

Objective To explore the effects of PKCε-ERK1/2 signaling pathway inhibitor on dural blood flow in a rat model of acute migraine.Methods Sixty adult male SD rats were randomly divided into 6 groups according to random number table method,with 10 rats in each group:control group(group N),Sham operation group(group S),migraine model group(group M),migraine model+dimethyl sulfoxide group(group DMSO),migraine model+PKCεinhibitor group(group H-7)and migraine model+ERK1/2 inhibitor group(group PD-98059).Immediately after modeling,the agents were injected into the lateral ventricle respectively.The change of dural blood flow was recorded by laser Doppler blood flow imager,and the percentage change of dural blood flow was compared in all group at 2 h after the modeling.Results There was no significant difference in percentage change of dural blood flow between group S and group N(P>0.05).Compared with group S,the percentage change of dural blood flow increased significantly in group M and group DMSO[(78.0±4.2)%vs.(3.8±1.0)%,(76.5±6.2)%vs.(3.8±1.0)%,all P<0.05].Compared with group M and group S,the percentage change of dural blood flow was significantly decreased in group H-7[(-24.8±4.9)%vs.(78.0±4.2),(-24.8±4.9)%vs.(3.8±1.0)%,all P<0.05].Compared with group M,the percentage change of dural blood flow was significantly decreased in group PD-98059,but significantly increased compared with group S[(29.4±3.9)%vs.(78.0±4.2)%,P<0.05;(29.4±3.9)%vs.(3.8±1.0)%,P<0.05].Conclusion Dural blood flow increases significantly during migraine attack in rats,and PKCεand ERK1/2 inhibitors could significantly reduce dural blood flow.