辛伐他汀减轻蛛网膜下腔出血后脑血管痉挛的机制研究

Analysis of the outcomes on severe traumatic brain-injured treated by different courses hyperbaric oxygen therapy

目的探讨辛伐他汀对兔蛛网膜下腔出血(SAH)模型脑血管痉挛(CVS)的保护机制。方法将48只新西兰大白兔随机分为3组:SAH组,通过二次枕大池注血建立SAH模型;辛伐他汀+SAH组(SAH+SVT组),连续7 d每日胃灌辛伐他汀5 mg/kg后建立SAH模型;假手术组,常规饲养,于相同时间点给予等量生理盐水。各组兔模型前后行两次灌注后取基底动脉组织制作病理切片,所有动物在第一次穿刺后第7天以免疫组化法检测动脉壁TNF-α蛋白的表达变化,ELISA法检测白介素-6(IL-6)、白介素-8(IL-8)水平,Western blot法检测壁e NOS蛋白表达的变化。结果免疫组化法检测基底动脉壁TNF-α表达结果显示,SAH+SVT组基底动脉痉挛减轻,与SAH组相比TNF-α表达明显降低(P<0.05);采用ELISA法检测基底动脉壁IL-6和IL-8水平,与SAH组相比SAH+SVT组基底动脉壁IL-6和IL-8水平均明显降低(P<0.05);采用Western blot法检测基底动脉壁内皮型一氧化氮合酶(e NOS)蛋白表达变化,与SAH组相比SAH+SVT组基底动脉壁e NOS蛋白表达明显降低(P<0.05)。结论辛伐他汀通过下调e NOS、TNF-α、IL-6和IL-8水平可减轻CVS。

Objective To discuss the protective mechanism of simvastatin on cerebral vasospasm （CVS） in rabbits with sub- arachnoid hemorrhage （SAH）. Methods 48 New Zealand rabbits were randomly divided into 3 groups： the SAH model group which was established by two cisternal injection, the simvastatin group ＋ SAH daily intragastric administration of simvastatin 5 mg/kg for 7 d after the establishment of SAH model;the operation group：conventional breeding, at the same time given normal saline. Before and after infu- sion, the pathological sections of basilar artery tissue were made, the expressions of TNF - alpha protein in the arterial wall of all animal in the first seventh days after puncture were detected by immunohistochemistry. The level of IL - 6, IL - 8 were used ELISA method to detect. The expression of eNOS protein was detected by Western blot. Result Immunohistochemical detection of basilar artery wall showed TNF - expression in SAH ＋ SVT group was reduced and there was statistical significance compared with the SAH group （ P 〈 0.05）, ELISA method was used to detect the level of IL - 6 and IL - 8 in basilar artery wall, compared with the SAH group, the level of IL - 6 and IL - 8 in SAH ＋ SVT group were decreased （P 〈 0.05）. The expression of eNOS protein in SAH ＋ SVT group was decreased significantly （P 〈 0.05 ）. Conclusions Simvastatin alleviates CVS by reducing eNOS, TNF - alpha, IL - 6 and IL - 8 levels.