法舒地尔降低TLR4表达缓解蛛网膜下腔出血后血管痉挛的实验研究

目的：建立兔蛛网膜下腔出血（SA H ）后迟发性脑血管痉挛（DCV ）模型，探讨法舒地尔防治DCV的作用及相关信号通路。方法60只新西兰大白兔分为3组，每组20只。实验组枕大池二次注血法建立S A H模型，对照组枕大池内注入生理盐水，治疗组SAH模型建立后，法舒地尔静脉给药。血管造影及经颇多普勒超声（TCD）评估血管痉挛情况，造模后第7天取材井行苏木素‐伊红染色观察基底动脉痉挛情况。免疫组织化学和Mestern blot方法检测基底动脉 Toll受体4（TLR4）的表达。结果SAH后血管痉挛模型造模成功，实验组与对照组比较基底动脉直径明显降低（P＜0．01）；治疗组基底动脉直径较实验组明显增加（P＜0．01）；免疫组织化学及 Mestern blot显示治疗组基底动脉 TLR4表达较实验组明显减少（P＜ 0．05）。结论 SAH后DCV可能与TLR4信号通路有关，法舒地尔能显著降低SAH后基底动脉TLR4表达，缓解SAH后DCV。

Fasudil relives cerebral vasospasm following subarachnoid hemorrhage by inhibiting TLR 4 expression

Objective To study the effect of Toll‐like receptor 4 inhibitor Fasudil on cerebral vasospasm after SAH .Methods A total of 60 New Zealand rabbits were randomly divided into three groups ,20 rabbits for each group ,SAH group:SAH model was established by autologous blood injection into the cisterna magna .Control group:saline was injected into cisterna magna .Fasudil group:Fasudil was injected into vein after SAH model .Vasospasm was valued by DSA and TCD .Seven days after operation basilar artery were collected .HE stain was used to observe vasospasm .TLR4 were observed by immunohistochemistry and western blot‐ting .Results Vasospasm model after SAH was successfully established .The basilar artery diameters were significantly shorter in the model group compared with the normal group (P<0 .01) .The artery diameter in Fasudil group increased significantly compared with SAH group(P<0 .01) .The expression of TLR4 decreased significantly in the Fasudil group compared with the model group (P<0 .05) .Conclusion Toll‐like receptor 4 pathway may be associated with cerebral vasospasm (DCV) .Fasudil could inhibit TLR‐4 expression and prevent cerebral vasospasm following subarachnoid hemorrhage .