乌司他丁对脂多糖诱导的大鼠肺组织Toll样受体4信号通路表达的影响

Effects of ulinastatin on toll-like receptor 4 signaling pathway in lung tissue of rats afterlipopolysaccharide insult

目的探讨乌司他丁对脓毒性大鼠肺损伤的保护机制。方法选健康清洁级SD大鼠30只，随机（随机数字法）分为生理盐水对照组10只、脂多糖（LPS）组10只、脂多糖＋乌司他丁（LPS＋UTI）组10只。注药24h后取肺组织观察形态学改变，分别应用RT-PCR或Westernblot及ELISA方法测定肺组织Toll样受体4（TLR4）、核因子-κB（NF-κB）及肿瘤坏死因子TNF-α mRNA及蛋白表达。结果脂多糖导致大鼠肺组织损伤，乌司他丁可下调肺组织TLR4 mRNA（t=3．563，P=0．032）、TNF-α mRNA（t=5．147，P=0．028）及TLR4蛋白（t=2．692，P=0．041）、NF-κB蛋白（t=2．459，P=0．024）、TNF-α．蛋白（t=3．336，P=0．037）表达，并减轻肺损伤。结论乌司他丁对脂多糖致肺损伤具有一定保护作用，其机制之一可能与抑制TLR4-NF-κB信号途径转导有关。

Objective To investigate the protective mechanisms of ulinastatin （UTI） in lung injury in septic rats. Methods Thirty healthy SD rats of clean grade were randomly （random number） divided into saline control group, lipopolysaccharide （LPS） group and lipopolysaccharide ＋ ulinastatin （ LPS ＋ UTI） group （n = 10, in each）. The lung tissues were obtained for morphological observation at the 24th-hour after LPS injection. RT-PCR or Western blot, ELISA methods were applied to measure the expressions of Toll-like receptor 4 （TLR4）, nuclear factor （NF） -κB, tumor necrosis factor （TNF） -α mRNA and their protein levels. Results LPS injection could result in lung injury. UTI could down-regulate the expressions of TLR4 mRNA （t = 3.563, P = 0. 032）, TNF-α mRNA （t = 5. 147, P = 0. 028）, TLR4 protein （t = 2. 692, P = 0. 041 ）, NF-κB protein （t = 2. 459, P = 0. 024） and TNF-α protein （t = 3.336, P = 0. 037） in lung, and could in turn alleviate lung injury. Conclusions UTI showed protective effects on LPS induced lung injury, and one of the mechanisms was perhaps associated with the inhibition of TLR4 - NF-κB signal transduction pathway.