TLR4在实验性脑出血小鼠脑组织表达变化及其与神经功能缺损的相关性

Upregulated expression of Toll-like receptor 4 in brain tissue surrounding hematoma correlates with neurologic deficits in experimental cerebral hemorrhage mice

目的探讨Toll样受体4(Toll-like receptor4,TLR4)在脑出血小鼠血肿周围脑组织中的表达变化及其与神经功能缺损的相关性。方法采用自体尾动脉血注入法复制脑出血小鼠模型,将30只雄性C57BL小鼠按照区组随机分组法分为假手术组、模型组,造模完毕后采取同样随机分组法根据不同时间点(术后6、24、48、72h,5d)分为5个亚组,每组3只。各组于不同时间点取材,采用荧光定量多聚酶链反应法(real-timePCR)检测小鼠脑组织TLR4mRNA的表达,同时测定神经功能缺损评分,并分析二者间的相关性。结果两组各时间点TLR4mRNA均表达;与假手术组相比模型组TLR4mRNA表达显著升高(P<0.05),且在72h达高峰。模型组相同时间点TLR4mRNA的表达与假手术组比较均明显增高,差异有统计学意义(P<0.05)。脑出血后神经功能缺损明显加重(P<0.05),以48～72h为著。相关分析显示,TLR4的表达与神经功能缺损呈直线相关(r2=0.973,P<0.05)。结论结果提示TLR4可能在脑出血后脑损伤中具有重要作用。

Objective To explore the expression of Toll-like receptor 4 （TLR4） in brain tissue surrounding hematoma of cerebral hemorrhage mice and the correlation between TLR4 and neurologic deficits. Methods The cerebral hemorrhage models of mice were made by injecting autologous arterial blood collected from caudal artery. Thirty male C57BL mice were randomly divided into 2 groups： sham-operation and model groups. Three mice of each group were killed for the brain tissue surrounding hematoma in 6, 24, 48,72 h and 5 d after operation respectively. The expression of TLR4 mRNA in the tissue samples was determined by real- time PCR, and neurologic deficits were determined at the same time points. The correlation of the expression and the deficits was analyzed. Results The expression of TLR4 gene in model group was higher evidently than that in sham-operation group （P 〈 0.05）. Cerebral edema and neurologic deficits were significantly increased, especially at 48 to 72 h after operation. Correlation analysis showed that there was a linear correlation of the expression of TLR4 and neurologic deficits （ r^2 = 0. 973, P 〈 0.05 ）. Conclusion TLR4 plays an important role in brain lesions of the cerebral hemorrhage, and maybe the key point of inflammatory reactions after intracerebral hemorrhage.