高血压脑出血大鼠脑组织TLR4、AQP-4、NO表达的变化及与脑水肿的关系分析

Changes of TLR4,AQP-4 and NO Expression in Brain Tissue of Hypertensive Intracerebral Hemorrhage Rats and Their Relationship with Brain Edema

目的:探讨高血压脑出血(HICH)大鼠脑组织中Toll样受体4(TLR4)、水通道蛋白-4(AQP-4)、一氧化氮(NO)表达变化情况及与脑水肿的关系。方法:选取48只SHR大鼠,随机分为假手术组、HICH 12h组、HICH 24h组、HICH 48h组HICH72 h组、HICH7d组,采用细菌胶原酶0.4U配成2μL,立体定向下注射至大鼠脑右侧尾状核建立HICH大鼠模型,假手术组注入等量生理盐水。观察相应时间点大鼠脑组织TLR4、AQP-4、NO表达变化情况及脑组织含水量变化情况,Pearson检验分析HICH大鼠脑组织含水量与脑组织中TLR4、AQP-4、NO表达情况的相关性。结果:各时间点HICH大鼠TLR4表达水平较假手术组均明显升高,其他时间点HICH大鼠TLR4表达水平较HICH 12 h组均明显升高(P<0.05);各时间点HICH大鼠AQP-4表达水平均较假手术组明显升高(P<0.05);各时间点HICH大鼠NO表达水平较假手术组均明显降低(P<0.05)。各时间点HICH大鼠脑组织含水量均较假手术组明显升高(P<0.05),且各组大鼠脑组织含水量呈升高后降低趋势(P<0.05)。Pearson检验结果显示HICH大鼠脑组织含水量与TLR4、AQP-4表达水平均呈正相关,与NO表达水平呈负相关(P<0.05)。结论:HICH大鼠脑组织TLR4、AQP-4、NO的动态变化与脑组织含水量具有相关性,提示三者参与了脑水肿的形成与消退,为后续临床针对HICH的诊疗方案制定提供新思路和方向,具备一定参考价值。

Objective:To investigate the expression of Toll like receptor 4(TLR4),aquaporin-4(AQP-4) and nitric oxide(NO) in the brain of hypertensive intracerebral hemorrhage(HICH) rats and their relationship with brain edema.Methods:48 SHR rats were randomly divided into sham operation group,hich 12 h group,hich 24 h group,hich 48 h group,hich 72 h group and hich 7 d group.Bacterial collagenase 0.4u was used to prepare 2 μL.The rat model of intracerebral hemorrhage was established by stereotactic injection into the right caudate nucleus of the rat brain.The sham operation group was injected with the same amount of normal saline.The expression of TLR4,AQP-4 and NO and the change of brain water content were observed at the corresponding time points.Pearson test was used to analyze the correlation between brain water content and the expression of TLR4,AQP-4 and NO in hich rats.Results:The expression level of TLR4 in hich rats at each time point was significantly higher than that in sham operation group,and the expression level of TLR4in hich rats at other time points was significantly higher than that in hich 12 h group(P<0.05).The expression level of AQP-4 in hich rats was significantly higher than that in sham operation group at each time point(P<0.05).The level of NO in hich rats was significantly lower than that in sham operation group at each time point(P<0.05).At each time point,the brain water content of hich rats was significantly higher than that of sham operation group(P<0.05),and the brain water content of rats in each group increased and then decreased(P<0.05).Pearson test showed that the brain water content of hich rats was positively correlated with the expression levels of TLR4 and AQP-4,and negatively correlated with the level of NO(P<0.05).Conclusion:The dynamic changes of TLR4,AQP-4 and NO in brain tissue of hich rats are correlated with brain water content,suggesting that they are involved in the formation and regression of brain edema,which provides new ideas and directions for the subsequent clinical diagnosis and treatment of hich.