大鼠脑出血模型血肿周围TLR4动态表达及其与脑水肿相关性

Dynamic expression of perihematoma Toll-like receptor 4 and its correlation with brain edema in rat model of cerebral hemorrhage

目的:探讨TLR4在大鼠脑出血模型血肿周围的动态表达及其与脑水肿的相关性。方法:采用自体尾动脉血注入法制作脑出血大鼠模型,将SD大鼠随机分为假手术组和手术组,每组分别于手术后1 h、6 h、1 d、3 d、5 d、7 d各取10只大鼠脑组织,采用免疫组化方法检测大鼠脑组织TLR4、TNF-α的表达,干湿重法测量脑水肿脑组织含水量。结果:同假手术组相比,手术组各时相点TLR4、TNF-α均表达升高(P<0.05),TLR4表达于6 h开始增多,3 d达高峰,5、7 d时有所下降;TNF-α表达于1 d时开始增多,3 d达高峰,5d时开始下降。手术组脑水肿脑组织含水量从6 h开始逐渐升高,至第3天时含水量达到最高峰,二者呈直线正相关(P<0.05)。结论:大鼠脑出血模型血肿周围TLR4表达上调,其可能参与脑出血后血肿周围脑水肿形成的炎性机制。

Objective:To investigate the dynamic expression of perihematoma Toll-like receptor 4(TLR4)in rat model of cerebral hemorrhage and its correlation with brain edema.Methods:Rat model of cerebral hemorrhage was established by injection of autologous caudal arterial blood.The SD rats were randomly divided into sham-operated group and operation group,and 10 rats from each group were harvested for brain tissues at 1 h,6 h,1 d,3 d,5 d and 7 d after the operation.Immunohistochemical assay was used to detect the expression of TLR4 and TNF-α in the rat brain tissues.The water content in the brain tissues was measured by dry/wet brain weight method.Results:Compared with the sham-operated group,the operation group showed increased expression of TLR4 and TNF-α at all time points(P<0.05);the expression of TLR4 started to increase at 6 h,peaked at 3 d,and showed some decline at 5 d and 7 d;the TNF-α expression started to increase at 1d,peaked at 3d,and began to decline at 5d.In the operation group,the water content in the edematous brain tissue gradually increased since 6 h until it peaked at 3 d.There was a positive linear correlation between TLR4 expression and brain edema(P<0.05).Conclusion:Perihematoma TLR4 is upregulated in rats with cerebral hemorrhage,and may be involved as part of inflammatory mechanism to the development of perihematoma brain edema after cerebral hemorrhage.