“以俞调枢”扶土抑木法对ROS-Nrf2-Keap1-ARE/NF-κB信号通路介导NASH机制研究

Non-alcoholic fatty hepatitis(NASH)is a key turning point in the progression from simple fatty liver to liver fibrosis.Due to the serious oxidative damage to free fatty acid β,reactive oxygen species(ROS)increases,so hepatic Kupffer cells are activated,which leads to IKK/NF-κB signaling pathway activating expressions of downstream inflammatory cytokines TNF-α,IL-6 and IL-1β; and activates the Nrf2-Keap1-ARE pathway to start expressions of heme oxygenase-1 (HO-1)and other antioxidant enzymes so as to fight inflammation, block the progress of NAFLD to NASH.The exact effects have been achieved by applying catgut embedding at Back-Shu point combined “Qiangganxiaozhi decoction” to treat NAFLD.So we propose a hypothesis that the therapy of "Regulating the pivot through the Back-Shu point" combined “Strengthening earth to inhibit wood” can prevent progress of NAFLD to NASH.In response to above-mentioned therapy,this project intends to replicate rat model of NASH,research the therapeutic mechanism of ROS activating cytokines TNF-α,IL-6 and IL-1βof NF-κB signaling pathway downstream,and Nrf2-Keap1-ARE signaling pathway activating HO-1 to prevent NAFLD progress.The aim of project research is to provide the scientific basis for applying Chinese medicine therapy of"Regulating the pivot through the Back-Shu point"combined“Strengthening earth to inhibit wood”to treat NASH through adjusting meridians outside and organs inside.

非酒精性脂肪性肝炎(NASH)是单纯性脂肪肝发展至肝纤维化的关键转折点。因游离脂肪酸β氧化严重受损，活性氧(ROS)增多，激活肝枯否细胞导致IKK/NF-κB信号通路活化下游炎症因子TNF-α、IL-6和IL-1β表达；并激活Nrf2-Keap1-ARE通路启动血红素加氧酶-1(HO-1)等抗氧化酶表达对抗炎症，阻断NAFLD进展为NASH。前期运用背俞穴位埋线联合“强肝消脂饮”治疗NAFLD，取得协同增效，故提出“以俞调枢”扶土抑木法法外调经络、内通脏腑防止NAFLD向NASH进展的假说。本项目拟复制NASH大鼠模型，探讨背俞穴位埋线联合“强肝消脂饮”对ROS激活NF-κB信号通路下游炎症因子TNF-α、IL-6和IL-1β，与Nrf2-Keap1-ARE信号通路活化HO-1抗氧化应激阻断NAFLD进展的效应机制，为中医“以俞调枢”扶土抑木法外调经络、内通脏腑防治NASH提供科学依据。

非酒精性脂肪性肝炎(NASH)是单纯性脂肪肝发展至肝纤维化的关键转折点。因游离脂 肪酸β氧化严重受损，活性氧(ROS)增多，激活肝枯否细胞导致IKK/NF-κB信号通路活化 下游炎症因子TNF-α、IL-6和IL-1β表达；并激活Nrf2-Keap1-ARE通路启动血红素加氧酶 -1(HO-1)等抗氧化酶表达对抗炎症，阻断NAFLD进展为NASH。前期运用背俞穴位埋线联合 “强肝消脂饮”治疗NAFLD，取得协同增效，故提出“以俞调枢”扶土抑木法法外调经络 、内通脏腑防止NAFLD向NASH进展的假说。本项目拟复制NASH大鼠模型，探讨背俞穴位埋 线联合“强肝消脂饮”对ROS激活NF-κB信号通路下游炎症因子TNF-α、IL-6和IL-1β， 与Nrf2-Keap1-ARE信号通路活化HO-1抗氧化应激阻断NAFLD进展的效应机制，为中医“以 俞调枢”扶土抑木法外调经络、内通脏腑防治NASH提供科学依据。