调气燥湿法调控抗氧化应激Keap1/Nrf2/ARE信号通路抑制肠“炎-癌”转化进展的效应机制

氧化应激在慢性肠炎癌变疾病进展的多阶段起着重要作用。在确认调气燥湿法防治肠癌有效的前提下并基于前期工作积累，本研究拟选取AOM/DSS诱导的慢性肠炎癌变小鼠模型，动态探究具有调气燥湿功效的芍药汤调控抗氧化应激信号通路Keap1/Nrf2/ARE发挥抗氧化作用对肠“炎-癌”转化进展的保护机制；体外建立氧化应激损伤、氧化应激炎性反应模型，探究氧化应激及氧化应激诱导的炎性反应对肠上皮细胞的损伤机制和芍药汤的保护机制。采用多种方法对氧化应激相关蛋白及抗氧化通路Keap1/Nrf2/ARE调控的多个蛋白HO-1、NQO1、UGT1A1、GSTM1进行检测；并对氧化应激诱导的炎性相关蛋白（p-NF-κB(p65)、p65、COX-2、iNOS）、增殖凋亡蛋白及炎性因子进行检测，系统探究氧化应激对肠炎癌变的影响，以期揭示调气燥湿法指导下的芍药汤抗氧化应激损伤防治肠炎相关性癌变的效应机制。

Oxidative stress plays an important role in multiple stages of colitis assocaited carcinoma. Based on the clinical effiency of Tiao-Qi-Zao-Shi method and our previous experimental data, AOM / DSS-induced chronic colitis carcinogenesis mouse model is chosen to explore the dynamic regulation roles of Shao-Yao-Tang on the oxidative stress signaling pathway, Keap1 / Nrf2 / ARE, and its anti-oxidant effects on the progression of chronic colitis transformation to carcinoma; In vitro experiments, oxidative stress model and oxidative stress induced inflammation model are established to explore the mechanisms of oxidative stress-induced inflammatory response to intestinal epithelial cell injury and the protection mechanisms of Shao-Yao-Tang drug serum. Using a variety of molecular biology methods to detect oxidative stress related proteins and the proteins from the key signal pathway with anti-oxidant role, Keap1 / Nrf2 / ARE, and its downstream targets, HO-1, NQO1, UGT1A1, GSTM1; oxidative stress-induced inflammatory related protein (p-NF-κB (p65), p65, COX-2, iNOS), proliferation and apoptosis proteins and inflammatory cytokines will be detected too. To comprehensive and systematic exploration of the impact of oxidative stress on chronic colitis associated carcinoma, reveals the molecular mechanisms of anti-oxidative stress of Shao-Yao-Tang under the guidance of Tiao-Qi-Zao-Shi method in colitis assciated carcinoma prevention and treatment, and supply practical evidence for colon cancer prevention and treatment.