脓毒症早期大鼠肝脏Toll样受体4基因表达及干预性研究

Intervention study on the hepatic expression of toll like receptor-4 in septic rats during the early phase

目的:探讨严重腹腔感染所致脓毒症大鼠肝脏Toll样受体4(Tolllikereceptor4,TLR4)基因表达变化规律及对其调节机制进行初步探讨。方法:采用大鼠盲肠结扎穿孔(CLP)模型造成脓毒症。将96只大鼠随机分为正常对照组、假手术组、CLP组、地塞米松(DXM)干预组,于CLP后2、4、6、12、24h处死动物,留取肝脏标本,以半定量逆转录多聚酶链反应技术及相关软件分析不同组TLR4mRNA、TNF鄄αmRNA的表达,检测血清丙氨酸转移酶(ALT)、天冬氨酸转氨酶(AST)及肝脏组织病理,评估肝脏损伤情况。结果:CLP组2h后肝脏TLR4mRNA、TNF鄄αmRNA及血清ALT、AST比正常对照组明显增多(P﹤0.01);DXM干预组各时间点TLR4mRNA、TNF鄄αmRNA的表达及血清ALT、AST较单纯CLP组显著降低(P﹤0.01),24h病理切片显示肝损伤轻于CLP组。结论:严重腹腔感染可致大鼠肝脏TLR4mRNA持续高表达,与肝脏的损伤密切相关;早期应用DXM可抑制TLR4mRNA的表达,减轻肝脏损伤。DXM抑制腹腔感染所致的炎症反应可能与抑制TLR4的表达有关。

Objective:To investigate the effects of Dexamethasone on the expression of hepatic Toll like receptors 4 mRNA after severe abdominal infection. Methods:Ninety-six male SD rats were randomly divided into four groups as follows:normal control group, sham operation group, cecal ligation and puncture group and DXM pretreated group. Rats were sacrificed at 2,4,6,12 and 24 h, the TLR4 mRNA and the TNF-α mRNA expressions in liver were measured at various intervals by reverse-transcription PCR. Meanwhile, the serum transaminases(ALT and AST) and the liver histopathology were detected. Results:The expression of TLR 4 mRNA was down-regulated in the DXM pretreated group, and the TNF-α mRNA was down-regulated significantly together with the TLR4 in comparison with the rats CLP alone(P < 0.01). The levels of ALT and AST in DXM pretreated group were much lower than that in CLP group(P < 0.01). Conclusion:Severe abdominal infection could lead to remarkable up-regulation of TLR4 mRNA expression in the liver, which might play an important role in the hepatic injury. DXM could inhibit the expression of TLR4 mRNA in the early phase of sepsis. The inhibitory effects of DXM on the inflammatory responses might be associated with the inhibition of TLR4 expression.