辛伐他汀对大鼠脑出血后TLR4介导的炎症损伤的干预作用  

Effect of simvastatin on inflammatory injury mediated by TLR4 after intracerebral hemorrhage in rats

作　　者：孟令丽[1] 周洪霞[1] 杨莎莎[1] 张作凤[1] 魏子峰[1] 张宇新[1] 田增有[1] 

机构地区：[1]河北联合大学基础医学院解剖教研室,唐山063000

出　　处：《神经解剖学杂志》2013年第5期557-561,共5页Chinese Journal of Neuroanatomy

摘　　要：目的:探讨辛伐他汀(simvastatin,SIM)对大鼠脑出血后Toll样受体4(toll-like receptor 4,TLR4)介导的脑内炎症损伤的干预作用。方法:采用注入自体血方法复制脑出血(intralerebral hemorrhage,ICH)模型,随机分为假手术组、模型组和干预组。Garcia等方法进行神经功能障碍评分;干湿重法检测脑组织含水量;免疫组化SP法检测TLR4和IL-1β蛋白的表达;免疫印迹检测TLR4和IL-1β蛋白的表达水平。结果:与假手术组比较,ICH模型组脑组织含水量明显升高(P<0.05),TLR4和IL-1β蛋白的表达明显增加(P<0.05);辛伐他汀干预后,TLR4表达量下降,IL-1β蛋白的表达及脑含水量明显下调,与脑神经功能障碍评分上调相一致。结论:大鼠脑出血后引起出血周围脑组织炎症损伤,辛伐他汀可能通过减轻TLR4介导的炎症损伤,改善神经功能恢复,起到神经保护作用。Objective： To study the effects of simvastatin on inflammatory injury mediated by TLR4 in intracerebral hemorrhage （ICH） rats. Methods： The ICH was induced by injection of autologous blood in rats. The rats were randomly divided into 3 groups, Sham group, ICH model group and treatment group. The behavioral changes were evaluated with Garcia＇ s neurologic deficit score. The water content of the brain was used to estimate the brain edema changes. Additionally, the expression of TLR4 and IL-1β was determined by immunohistoehemistry and Western blot. Results： In model group, the water content of brain in cerebral tissues was higher than that in the Sham group （ P 〈 O. 05 ）. The expression of TLR4 and IL-1β markedly increased after intraeerebral hemorrhage （ P 〈 0.05 ）. Compared with the model group, administration of simvastatin significantly inhibited the expression of IL-1β and TLR4, reduced the water content of brain, and coincided with the improvement of neurologic deficit score. Conclusion： Our findings indicate that administration of SIM has a neuroprotective effect against cerebral hemorrhage, which may be related to the suppression of inflammatory injury mediated by TLR4, and there fore promote the recovery of neural function.

关 键 词：脑出血 辛伐他汀 TLR4 IL-1Β 

分 类 号：R965[医药卫生—药理学]