TLR4在急性肝衰竭模型大鼠中的动态变化及意义

DYNAMIC CHANGES AND SIGNIFICANCE OF TOLL-LIKE RECEPTOR 4 IN THE RAT MODEL OF ACUTE LIVER FAILURE

目的探讨TLR4在D-Gal/LPS诱导的大鼠急性肝衰竭中的表达变化及其作用。方法65只SD雄性大鼠随机分为正常对照组(n=5)、D-Gal/LPS模型组(n=25)、PDTC干预组(n=25),于不同时间点检测肝功能,免疫组化观察肝组织TLR4的表达,TUNEL法观察肝脏细胞凋亡。结果模型组大鼠4h开始ALT、AST明显升高,8h达峰值,4-24h ALT、AST明显高于正常对照组(P<0.05)。模型组各时间点TLR4表达明显高于正常对照组(P<0.05)。模型组凋亡的肝脏细胞数随时间的延长逐渐增多,均高于正常对照组(P<0.05)。PDTC干预后ALT、AST水平,TLR4的表达及凋亡的肝脏细胞数低于模型组(P<0.05)。结论急性肝衰竭模型鼠TLR4表达增强,PDTC干预可下调其表达,提示TLR4在急性肝衰竭的发生发展中可能具有一定作用。

Objective To explore the expression LPS-induced rat model of acute liver failure. Methods and the role of TLR4 in the liver of the D-Gal and 65 male SD rats were randomly divided into three groups： normal control group （n=5）, model group （n=25） and PDTC treatment group （n=25）. Serum transaminase （ALT and AST） and TLR4 in the liver and the apoptosis of liver cells were determined at 2, 4, 8, 12, 24 hours after injection of D-Gal/LPS. Results The serum transaminase level was elevated at 4 hour, peaking at 8 hour, significantly higher than that of the normal control group at 4, 8, 12, 24 hours after injection of D-Gal/LPS （P〈0.05） . TLR4 was expressed at a higher level in the model group （compared with the normal control group, P〈0.05）. The number of apoptotic cells in the liver increased gradually, which was higher than that of the normal control group （P〈0. 05）. However, after treatment with PDTC, serum transaminase level, the expression of TLR4 and the number of apoptotic cells in the liver were lower than those of the model group （P〈0. 05）. Conclusion The expression of TLR4 in liver tissue was increased by D-Gal/LPS, which can be down-regulated by PDTC pretreatment. It is indicated that TLR4 might be involved in acute liver failure.