Toll样受体4拮抗剂防治兔蛛网膜下腔出血后迟发型血管痉挛

目的 探讨Toll 样受体4（Toll like receptor 4，TLR4） 拮抗剂依立托仑四钠（E5564） 防治蛛网膜下腔出血（subarachnoid hemorrhage，SAH） 后迟发性脑血管痉挛（delayed cerebral vasospasm，DCV） 的作用。 方法 新西兰大白兔60 只随机分为3 组，每组20 只。模型组枕大池二次注血法建立SAH 模型。对照组枕大池内注入0.9% 氯化钠注射液。E5564 组SAH 模型建立后，E5564 静脉给药。血管造影及经颅多普勒评估血管痉挛情况，造模后第7 天取材，HE 染色观察基底动脉痉挛情况。免疫组化和Western blot 方法检测基底动脉Toll 受体4 的表达。 结果 SAH 后血管痉挛模型造模成功，模型组与对照组比较基底动脉直径明显降低（P ＜ 0.01） ；E5564 组基底动脉直径较模型组明显增加（P ＜ 0.01） ；免疫组化及Western blot 显示E5564组基底动脉TLR4 表达较SAH 组明显减少（P ＜ 0.05）。 结论 蛛网膜下腔出血后迟发型脑血管痉挛可能与Toll 样受体4 信号通路有关，E5564 可以明显降低SAH 后基底动脉TLR4 表达，缓解SAH 后迟发型脑血管痉挛。

Effect of Toll-like receptor 4 inhibitor on delayed cerebral vasospasm following subarachnoid hemorrhage

Objective To study the effect of Toll-like receptor 4 （TLR4） inhibitor E5564 on delayed cerebral vasospasm （DCV） following subarachnoid hemorrhage （SAH）. Methods Sixty New Zealand rabbits were randomly divided into SAH model group, control group and E5564 group （20 in each group）. Blood was injected into the animal cisterna magna of SAH model group, saline was injected into the animal cisterna magna of control group, and E5546 was injected into the animal vein of E5564 group after the SAH model was established. DCV was assessed by angiography and TCD, respectively. Basilar artery spasm was observed with HE staining 7 days after the SAH model was established. Expression of TLR4 in basilar artery was detected by immunohistochemistry and Western blot, respectively. Results The diameter of basilar artery was significantly shorter in SAH model group than in control group and significantly longer in E5564 group than in SAH model group （P 〈 0.01）. Immunohistochemistry and Western blot showed that the expression level of TLR4 in basilar artery was significantly lower in E5564 group than in SAH model group （P 〈 0.05）. Conclusion DCV following SAH may be associated with the TLR4 signal pathway. E5564 can significantly inhibit the expression of TLR-4 in basilar artery, thus alleviating DCV following SAH.