Toll样受体4和肿瘤坏死因子-α在脑出血大鼠血肿周围脑组织的表达

Expressions of TLR4 and TNF-α around the hematoma following intracerebral hemorrhage in rats

目的:探讨大鼠脑出血(ICH)后脑水肿情况及其血肿周围Toll样受体4(TLR4)和肿瘤坏死因子-α(TNF-α)的动态表达情况.方法:采用注入自体血方法复制脑出血模型,SD大鼠随机分为假手术组和模型组(ICH 12 h、ICH 24 h、ICH 72h及ICH 7 d).干湿重法检测各时间点脑组织含水量(BWC);尼氏染色观察脑组织病理学变化;免疫组织化学检测TLR4、TNF-α蛋白的表达变化;免疫印迹检测TLR4、TNF-α蛋白的表达水平.结果:脑出血后脑含水量较假手术组明显增加;ICH模型组神经细胞内尼氏体丢失明显;脑组织血肿周围TLR4和TNF-α在脑出血后12h开始表达,随时间延长蛋白表达增加,3d达到高峰,随后表达降低.结论:大鼠脑出血后TLR4的大量激活可能进一步诱导了TNF-α的表达,加重了脑出血后的继发性炎症损伤和脑水肿的形成.

Objective:To investigate the expressions of Toll-like receptor 4(TLR4) and tumor necrosis factor-alpha(TNF-α)around the hematoma and their correlations with cerebral edema in rat brain after experimental intracerebral hemorrhage(ICH).Methods:SD rats were randomly divided into sham-operated group and ICH model groupsGCH 12 h,ICH 24 h,ICH72 h and ICH 7 d).The intracerebral hemorrhage model was induced by injection of autologous blood in rats.The water content of the brain was measured with dry/wet weight method.Histopathological changes were determined by Nissl’s staining.Additionally,the expressions of TLR4 and TNF-α were determined by immunohistochemistry and Western blotting.Results:In the model group,the water content of the brain in cerebral tissues was higher than that in the sham group.Nissl’s bodies of nerve cells in ICH model groups were obviously lost.TLR4 and TNF-α appeared at 12 h,then they gradually increased and reached the maximum at 3 d,and decreased after 72 h,but they were significantly higher than those in the control group.Conclusion:High expression of TLR4 in the rats of ICH model groups show that activated-TLR4 can aggravate inflammatory reactions by inducing TNF-α expression,and take part in the pathological process of brain edema.