基于糖脂代谢异常致病机制研究肝病传脾的基因本质

glycolipid metabolic disorder characterized by energy excess was common cause of non-alcoholic fatty liver (NAFLD) and type 2 diabetes. Due to differences in physiological functions of glucose and lipid, the fat excess showed off firstly in the pathogenic process of energy excess，and then it caused NAFLD which belongs to GAN-PI disease in TCM and was located in the liver.Following this, insulin resistance and islet dysfunction caused by NAFLD and lipid toxicity, which acted as transmission way, damaged glycometabolism to produce impaired glucose regulation，that was pre-diabetes which belongs to PI-DAN disease in TCM and located in the spleen. If timely treatment of liver disease and simultaneously strengthening of spleen(zhi-gan shi-pi) in the GAN-PI disease stage,the transmission way could be prevented and that will reduced pre-diabetes to occur. according to the pathogenic characteristics of metabolic disorder in Chinese, differentially expressed genes responsibilities of each stage in the pathogenic process of Gan-bin-chuan-pi will be identified by microarray technology. And then they will be identified reversedly by treatment of zhi-gan shi-pi, so that the gene essence of Gan-bin-chuan-pi will be found out. In four subsequent cell experiments with qPCR, Western blot, ELISA techniques etc., we will deeply research expression of mRNAs of genes related to adipogenesis，insulin resistence, islet function and energy metablism found out in the aforementioned genetic analysis, and also study their regulator in upper reach , as well as regulated factors in the down reach and their effects.The study will provide a scientific basis for prevention and treatment of metabolic disease according to classical Chinese medicine theory of Gan-bin-chuan-pi.

以能量过剩为特征的糖脂代谢异常是非酒精性脂肪肝（NAFLD）和2型糖尿病的共因。因糖、脂生理功能的差异，能量过剩首先表现为脂肪过剩进而产生NAFLD（中医为肝僻，病位在肝）。继以NAFLD及脂毒性诱生胰岛素抵抗和胰岛功能减退为介导(传变路径），损伤糖代谢而发生糖调节受损（糖尿病前期，中医为脾瘅，病位在脾）。如在肝僻阶段及时治肝实脾，可调控此传变过程而预防糖尿病前期的发生。本项据我国人群致病特点，以基因芯片技术首先找出肝病传脾过程各阶段的差显责任基因，再以治肝实脾法反证，找出肝病传脾基因本质。后续四个细胞实验用qPCR、Western blot、ELISA等技术，对前述基因分析找出的成脂相关本质基因、胰岛素抵抗相关本质基因、胰岛功能相关本质基因、能量代谢调节相关本质基因的mRNA表达及其上游调节因素、下游被调节因素和效应等，逐一深入研究。为按肝病传脾经典理论防治代谢性疾病提供科学依据。

以能量过剩为特征的糖脂代谢异常是非酒精性脂肪肝（NAFLD）和 2 型糖尿病的共因。因糖、脂生理功能的差异，能量过剩首先表现为脂肪过剩进而产生 NAFLD（中医为肝僻，病位在肝）。继以 NAFLD 及脂毒性诱生胰岛素抵抗和胰岛功能减退为介导(传变路径），损伤糖代谢而发生糖调节受损（糖尿病前期，中医为脾瘅，病位在脾）。本项目预实验建立了肝病传脾的代谢病模型，动物实验阶段检测血糖、胰岛素、血脂水平等代谢相关因素，并运用全基因组工程技术代谢病肝病传脾存在成脂基因、能量代谢基因、胰岛功能基因、胰岛素抵抗基因的异常表达，并通过细胞实验对相关基因进行了验证，干预这些基因的表达阻滞了肝病传脾的发展。提示这些异常表达的基因可能是代谢病肝病传脾的基因本质。