中文摘要
原发性肝癌发病率逐年上升,HBV感染和乙醇性肝病是其两大危险因素。肿瘤微环境已被作为癌前状态或HCC患者的关键性治疗靶点,阻止肝脏微环境中新生血管生长可作为阻止肿瘤进展的一项重要策略。中医药在肝癌治疗上的优势越来越受到重视。前期研究表明,葛花解酲方可调控p27等血管平滑肌增殖因子以及APC等Wnt信号通路重要分子。基于此提出科学假说:葛花解酲方可能通过协同调控VEGF和Wnt信号转导通路、改善肝脏微环境、阻断血管新生,达到抑制肝癌发生发展的作用。课题组创新性引入微循环活体动态可视化技术配合活体光学成像技术,再加上形态学、分子生物学方法,更立体、更直观、更系统地评价葛花解酲方对乙醇性HBV转基因小鼠肝脏微环境血管新生的抑制作用,探讨其协同调控VEGF和Wnt信号通路的分子机制;并从肝脏微环境血管新生的新视角去阐释“肝藏血主疏泄”功能失常对肝癌的影响,丰富臧象理论的科学内涵。
英文摘要
The incidence of Primary liver cancer increases year by year, HBV infection and alcoholic liver disease are the two major risk factors. The tumor microenvironment has been considered as a precancerous condition or key therapeutic target for HCC patients, it is an important strategy used as to prevent tumor progression to block the growth of new blood vessels in liver microenvironment. The advantages of traditional Chinese medicine in the treatment of liver cancer get more and more attention. Previous studies have shown that Gehuajiecheng Decoction can regulate Vascular smooth muscle cell proliferation factor such as p27 and important molecules in Wnt signal pathway, like APC. So we put forward the scientific hypothesis based on this: Gehuajiecheng Decoction may inhibit liver cancer development by coregulating VEGF and Wnt signal transduction pathway, improving the liver microenvironment and blocking the vascular newborn. The research group introduces innovatively the visualization technology of vivo microcirculation dynamic coordinated with vivo optical imaging technology and couples with the morphology, molecular biology methods, which makes us more stereoscopic, intuitive, and systematic to evaluate that how dose Gehuajiecheng Decoction inhibit the angiogenesis of liver microenvironment in ethanol HBV transgenic mice, and to explore its molecular mechanism of regulation of VEGF and Wnt signaling pathway synergisticly. We even explain the effect of dysfunction of liver storeing blood and governing free flow of qi on liver cancer from a new perspective of microenvironment of the liver angiogenesis, which riches the scientific connotation of the Zang theory.
