基于LXR-AVP/RAAS复杂式调控通路的慢性心力衰竭“温阳消饮”法多靶点疗效作用机制研究

慢性心力衰竭（CHF）属中医痰饮范畴，温阳消饮法是该病证经典有效治法，其作用机制值得进一步探索。前期自然基金课题研究发现：温阳消阴法可显著改善CHF大鼠RAAS系统过度激活、心肌重塑及肺、肾组织多种水通道蛋白表达异常，基因芯片检测示该治法差异表达基因主要与脂肪细胞因子通路等相关。转录因子LXR作为脂肪细胞因子通路下游调节靶点，通过LXR-AVP-AQPs调节机体水液平衡，并对RAAS系统有多靶点效应，最终改善心肌重塑。本课题在痰饮理论认识指导下，以转录因子LXR调控基因表达时空多态性为切入点，密切围绕“LXR-AVP/RAAS复杂式调控通路参与调节CHF小鼠水液平衡和神经内分泌机制从而改善心肌重塑是温阳消饮法治疗CHF多靶点疗效的关键核心机制”假说开展研究。拟采用LXR敲除小鼠、EMSA等生物学技术，探索该法的CHF多靶点疗效关键核心机制，为阐释痰饮理论及温阳消饮治法的科学基础提供实验依据

Abstract：Chronic heart failure（CHF）is classified as Traditional Chinese medicine（TCM） phlegm Category.Numerous clinical and experimental studies confirm: Wen Yang Xiao Yin therapy is the classic effective treatment method of the syndrome,and the mechanism is Worthy of further exploration. Supported by the the early Natural Science Foundation Project findings, Our group found that Lingguizhugan and Tinglidazaoxiefei decoction,as the representative prescription of the therapies,can significantly improve the CHF rats excessive activation of RAS system, cardiac remodeling ,and abnormal expression of aquaporin in lung, kidney and other tissues,and the microarray shows the differentially expressed genes mainly related adipokines pathways. As the transcription factor, LXR is the downstream regulatory targets of the adipocytes pathway, Regulating the body's fluid balance by the LXR-AVP-AQPs pathway,and multi-target effecting on the RAAS system, and ultimately improve myocardial remodeling. Based on this, under the guidance of the TCM phlegm theory,the research will use an entry point that transcription factor LXR regulate gene expression in space-time polymorphism, and be carried out closely around the hypothesis "LXR-AVP / RAAS complex pathways involved in the regulation of CHF mouse liquid water balance and neuroendocrine mechanisms to improve cardiac remodeling is the critical core mechanism of Wenyangxiaoyin treatment ‘s multi-target effect on CHF".Intending to adopt FXR knockout mice, ELISA and other biological techniques,the research explore the critical core mechanism of Wenyangxiaoyin treatment ‘s multi-target effect on CHF, provide the scientific basis for experimental basis To illustrate the theory of phlegm and Wenyangxiaoyin treatment.