基于TLR-4/NF-κB信号通路探讨解毒化瘀扶正法治疗内毒素性肺损伤的作用机制

项目名称： 基于TLR-4/NF-κB信号通路探讨解毒化瘀扶正法治疗内毒素性肺损伤的作用机制

项目编号： No.81202675

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 马宏博

作者单位： 山东大学

项目金额： 23万元

中文摘要： 急性肺损伤是严重创伤或感染出现的一种失控性炎症反应综合症，TLR4/NF-κB是与机体免疫及炎症反应最为密切的信号通路。解毒化瘀扶正法符合急性肺损伤的中医辨证思路，可有效调控炎症反应。本课题研制加味清营颗粒（清营汤加西洋参、大黄），观察对内毒素性肺损伤大鼠模型血浆中炎症因子及肺组织NF-κB、TLR4mRNA、AQP-1、NF-κB 及TLR4蛋白的影响；运用RNA干扰技术，研究TLR4/NF-κB信号通路在LPS诱导的大鼠肺损伤中的表达与作用，并进一步通过含药血清对大鼠肺泡巨噬细胞系NR8383炎症因子分泌的影响及TLR4和NF-κB 亚基P65 mRNA及蛋白表达影响的实验，揭示解毒化瘀扶正法对内毒素性肺损伤TLR-4/NF-κB信号转导通路的影响。本课题率先研究从多方面、多层次来探讨加味清营颗粒对内毒素性肺损伤的作用及机制，为临床开发新药打下基础。

中文关键词： 加味清营颗粒；内毒素性肺损伤；TLR4/NF-κB；信号通路；

英文摘要： Acute lung injury is one of uncontrolled inflammatory syndrome after severe trauma or infection, and the TLR4/NF-κB signal passage is most closely related to the immune and inflammatory response. The therapy of detoxifying and clearing stasis with righting is more suitable to the considerations on Chinese Medical Syndrome Differentiation of acute lung injury, and can regulate inflammatory response effectively. This topic develops the Modified Qingying Granule (Qingying decoction together with american ginseng and rhubarb), and observes the effects on the inflammatory factor in the plasma and the the expression of NF-κB、TLR4mRNA、 AQP-1、NF-κB and TLR4 protein in the lung tissue of the rat model of endotoxin induced lung injury; researches on the expression and role of TLR4/NF-κB signal pathway in LPS-induced rat lung injury by RNA interference technique, and through further in vitro experiment that observes the effects of drug-containing serum on LPS-induced rat alveolar macrophage cell line NR8383 inflammatory cytokine secretion and the effects on the expressions of TLR4、NF-κB subunit P65 mRNA and protein, to reveal the effects of the therapy of detoxifying and clearing stasis with righting on TLR-4/NF-κB signal passage of endotoxin induced lung injury. This topic leads the research work about the function and me

英文关键词： Modified Qingying Granule；Endotoxin Induced Lung Injury；TLR4/NF-κB；Signal Passage；