基于TLR4/NF-κB通路的解毒化瘀通腑法干预内毒素性肝损伤的作用机制

项目名称： 基于TLR4/NF-κB通路的解毒化瘀通腑法干预内毒素性肝损伤的作用机制

项目编号： No.U1504825

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘江凯

作者单位： 河南中医药大学

项目金额： 27万元

中文摘要： 在急、慢性重型肝炎、肝硬化等患者中, 往往合内毒素血症，内毒素血症是导致病情急剧进展、难以逆转的最主要因素之一。TRL4/NF-κB是内毒素所致肝损伤中起关键作用的信号转导通路。目前临床尚无有效治疗内毒素血症的药物，前期工作显示解毒化瘀通腑法能有效的改善肝功能，延缓病情进展，但缺乏进一步作用机制的研究。因此本课题以TRL4/NF-κB信号通路为主线，通过解毒化瘀通腑法干预内毒性肝损伤大鼠模型，观察肝组织病理改变，炎症因子TNF-a、IL-1β、IL-6及内毒素水平变化；解毒化瘀通腑法对TRL4/NF-κB通路上下游关键分子CD14、TLR4、MyD88、IKK、NF-κB表达的影响，以论证解毒化瘀通腑法是通过影响TRL4/NF-κB通路炎症级联信号的传递，抑制NF-κB的激活，减轻内毒素对机体损害的假说，探讨其干预内毒素性肝损伤的作用机制，更深入认识中医药治疗内毒素血症的优势环节和机理。

中文关键词： 中医药疗法；肝损伤；炎症因子；信号通路；作用机制

英文摘要： In patients with acute and chronic severe hepatitis,cirrhosis of the liver and so on, tend to merge endotoxemia,Endotoxemia is one of the main factors leading to the disease rapidly progress and difficult to reverse.TLR4/NF-κB signal transduction pathway plays a key role in endotoxin-induced liver injury.At present there is no effective drugs for the treatment of endotoxemia, preliminary work shows jiedu huayu tongfu method can effectively improve liver function, delay the progress of the disease,but the lack of further study on mechanism of action. Therefore , the issue with TLR4/NF-κB signal pathway as the main line, through the jiedu huayu tongfu method intervene endotoxin-induced liver injury model in rats,to observe the liver tissue pathological changes and the changes of inflammatory factors TNF-a, IL-1β, IL-6 and endotoxin level;Effect of expression about jiedu huayu tongfu method on TLR4/NF-κB pathway upstream and down stream molecule CD14, TLR4, MyD88, IKK, NF-κB,In order to prove the hypothesis of jiedu huayu tongfu method is affected by the transmission of TLR4/NF-κB inflammatory cascade signal pathway, inhibiting activation of NF-κB, alleviate the damage of endotoxin on body, to explore the mechanism of jiedu huayu tongfu method intervention in endotoxin-induced liver injury, further understand the dominant part and curative mechanism of Chinese medicine for the treatment of endotoxemia.

英文关键词： Traditional Chinese medicine therapy;Liver injury ;Inflammatory factor;Singal pathway;Mechanism of action