TOLL样受体4及细胞因子在致大鼠发病机制中的作用

The effect of Toll like receptor 4 and cytokines on the pathogenesis of epilepsy model in the rats

目的探讨海马组织中TOLL样受体4(TLR-4)和白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)及白细胞介素10(IL-10)在致大鼠发病机制中的作用。方法应用戊四氮(PTZ)腹腔注射建立大鼠致模型后,观察大鼠致过程中的行为学变化,分别于14、21、28和35 d留取大鼠海马组织,用酶联免疫吸附测定方法(ELISA)检测海马组织中TLR-4、IL-1β、TNF-α和IL-10的蛋白含量,用实时荧光定量PCR方法检测海马组织中TLR-4 mRNA的表达水平。结果随着致时间的延长,大鼠癫发作程度逐渐加重,但是致痫间30 d后癫发作程度有所减轻。随着癫发作的进展,海马组织中TLR-4、IL-1β、TNF-α和IL-10的蛋白含量逐渐升高(P<0.01),海马组织中TLR-4 mRNA表达水平明显增强(P<0.05或P<0.01),而在35d有所下降。TLR-4的蛋白含量与IL-1β、TNF-α和IL-10含量呈正相关(P<0.01)。结论 TOLL样受体4表达增强及炎症因子和抗炎因子的表达失衡在致发病过程中发挥着重要作用。

To investigate the effect of Toll like receptor 4 （TLR-4） and interleukin 1β （IL-7 113）, tumor necrosis factor a （TNF-a） and interleukin 10 （IL-10） on the pathogenesis of epilepsy model in the rats. Methods The epilepsy model was induced by intraperitoneally injecting into the rats with pentylenetetrazol （PTZ）, and the behavior change in the process of seizure was observed. In the 14d.21d.28d and 35d, hippocampus were collected, and the protein expressions of TLR-4, IL-1β, TNF-α and IL-10 were examined by ELISA. The expression of TLR-4 mRNA were detected by realtime PCR. Results With the progress of epilepsy, the degree of epileptic seizures in the rats increased gradually, however, after 30d, the seizure re duced slightly; the levels of TLR-4, IL-1β,TNF-α and IL-10 increased significantly （P〈0. 01 ）, the expression of TLR-4 mRNA decreased gradually（P%0. （15 or P%0. 01）, in 35d declined. Pearson correlation analysis showed that the level of TLR-4 was positively correlated with IL-1β, TNF-α in hippocampus tissue,and correlated negatively with IL-10 （P %0. 01 ）. The expression of TLR-4 mRNA decreased gradually（P%0. 01）. Condusions The enhanced expression of TLR-4 as well as the imbalance between the proinflammatory and anti in flammatory cytokine plays a pivotal role in the pathogenesis of chronic epilepsy.