基于胆固醇"吸收-合成-外排"平衡调控的降脂宁治疗高胆固醇血症的机制与效应成分研究

Hypercholesterolemia has high incidence and caused great harm to us, it is also an independent risk factor for cardiovascular disease and many other complex disease. Although medicine for this disease were designed and achieved a certain effect, but the prevalence of gastrointestinal side effects, liver toxicity and other adverse reactions happened as common.It is certain that the combination of 2 or 3 drugs may have a higher efficacy，while the side effect increase significantly. Our previous studies suggested that as the protect species herb which contained in "Chinese Pharmacopoeia”, Jiangzhining can effectively reduce cholesterol levels both in synthesis and metabolic aspects. Combined with in vitro cell experiments validation, this project intends to use lipid genomics technologies, to investigate the effect of Jiangzhining on cholesterol absorption, synthesis and transformation, and eventually find the targets of Jiangzhiing on high cholesterol and ingredients that mattered. Our final purpose is to reveal Jiangzhining regulating the hypercholesterolemia from cholesterol absorption synthesis - transport and the whole process, and thus to get the mechanism of Jiangzhining effect on three levels.

高胆固醇血症发病率高，危害性大，是心血管病等许多重大复杂疾病的独立危险因子。西药针对该病虽取得了一定的疗效，但普遍存在胃肠道副作用、肝毒性等不良反应，且单用效果不理想，联合用药副作用增大。课题组前期研究提示，降脂宁能够在合成和代谢环节有效的降低胆固醇水平。本项目拟采用脂类代谢组学、药物代谢组学和整体、离体细胞实验相结合的方式，以胆固醇“吸收-合成-外排” 整体代谢为基础，探究降脂宁调控高胆固醇血症的作用靶点与效应成分。并通过细胞实验进一步探究各个效应成分的主要作用靶点和机制，全面系统揭示降脂宁调控胆固醇代谢全过程“分子-细胞-整体动物”三个层面的作用机制。

高胆固醇血症发病率高，危害性大，是心血管病等许多重大复杂疾病的独立危险因子。西药针对该病虽取得了一定的疗效，但普遍存在胃肠道副作用、肝毒性等不良反应，且单用效果不理想，联合用药副作用增大。课题组研究表明，降脂宁能够在合成和代谢环节有效的降低胆固醇水平。本项目采用脂类代谢组学、药物代谢组学和整体、离体细胞实验相结合的方式，以胆固醇“吸收-合成-外排” 整体代谢为基础，探究降脂宁调控高胆固醇血症的作用靶点与效应成分,实验得出：高剂量组可降低血脂水平，保护血管内皮并具有改善肝肾功能的作用。代谢组学分析得出：降脂宁使实验大鼠的肝脏代谢物物质水平有恢复正常的趋向和效果，并对肝脏潜在生物标志物进行鉴定，代谢通路分析得出：降脂作用可能与叶酸一碳代谢通路和戊糖葡萄糖醛酸转换通路这两条通路相关。通过细胞实验进一步得出降脂宁对HMG-CoA还原酶酶活性的具有一定的抑制效果。