基于蒙医“精华与糟粕分解”理论的连翘-4抗肝损伤基因组学和蛋白组学作用机制研究

Since ancient times, Mongolian people lived a nomadic, hunting, living by all the year round and the cold, damp, snow and other natural disasters. Therefore, their living habits such eating and living condition, environment, climate and other factors influence of Mongolian medicine clinical liver, stomach, digestive system diseases.Previous studies have found that 168 differences proteins and 562 genes from pyloric ligation induced hepatic injuries animal model. The “lianqiao- 4” prescription has certain adjustment of the liver tissue PXR, CAR nuclear receptors and MRP3, MRP4 membrane protein and has obvious improvement effects the various indicators of the pylorus ligation induced liver injury model. .Evaluate to “lianqiao-4” prescription`s action mechanism of the gene and protein biomarkers for the model through genomics and proteomics analysis.According to Mongolian traditional medicine holistic view, there has correlation of the stomach, liver and small intestine for assumptions. Pylorus ligation in rats caused to its peptic ulcer disease and fail to liver function, and even cause duodenal ulcer model.For clinical application of “lianqiao-4” further scientific explanation lay conditions, effect on hepatic pyloric ligation of biological information network pharmacology, provide reliable experimental data for the study of the modernization of the formulas.

自古以来，蒙古族人民过着逐水游牧、狩猎生活，常年与寒冷、潮湿、风雪等自然灾害做斗争。因此，由于饮食、起居习惯、环境气候和其他因素等缘故蒙医临床上肝脏、胃为首的消化系统疾病较多。前期研究发现“幽门结扎”性肝损伤动物模型测到168个差异蛋白和562个差异基因，且方药连翘-4对该模型各种指标的改变具有明显的好转作用，对肝组织PXR、CAR核受体和MRP3、MRP4膜蛋白具有一定的调节作用。.拟申报课题以蒙医“整体观”为依据，胃、肝脏和小肠的相关性为假设，建立大鼠“幽门结扎”引起胃酸过多而导致“胃溃疡”，进一步诱发“肝功能异常”、甚至引起十二指肠溃疡模型，选择连翘-4为示例方药，采用基因组和蛋白组学方法分析该方药对此模型的作用机制，寻找基因、蛋白生物标志物。为连翘-4临床应用的进一步科学解释奠定条件，对幽门结扎性肝损伤作用的系统生物信息网络药理学提供可靠的实验数据，为方药现代化研究提供思路。

1.研究背景：.本课题是以蒙医“三根七素”理论为基础，“整体观”为导向，“精华与糟粕分解”来贯穿机体新陈代谢全过程为理论背景。.2.主要研究内容： .（1）幽门结扎性肝损伤模型的建立；（2）连翘-4 对幽门结扎性肝损伤保护作用研究；（3）连翘-4 对幽门结扎性肝损伤保护作用基因组学研究；（4）连翘-4 对幽门结扎性肝损伤保护作用蛋白组学研究。 .3.重要结果及关键数据：.“胃—肝—小肠”相关性通路和靶点，并连翘-4通过调节该通路和靶点达到“精华与糟粕分解”平衡的目的。相关通路和靶点如下：.①基因组学：胃（Retinol metabolism ：Ugt2b1、Cyp2b2 ）—肝脏（Metabolicpathways：Bcat1、Dhrs3）—小肠（Complement and coagulation cascades ：Casq1、Masp1）；② 蛋白质组学：胃（Ribosome：RPL35、RPL37；Alcoholism：LOC102548682）—肝脏（Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)：Igfbp1；Glutamate Neurotransmitter Release Cycle：Slc38a2）—小肠（Amoebiasis：Serpinb1a、Serpinb6a；Syndecan interactions：Vtn）。.4.科学意义：.①阐明了“胃”、“肝脏”、“十二指肠”之间的生理“连贯性”和蒙医“整体观”思维指导下的“精华与糟粕分解”理论现代科学内涵；②连翘-4 对幽门结扎致肝损伤作用的基因、蛋白生物标志物；③解释了该药在蒙医临床应用机制。