Establishment Of LDLR Agonist Model & Its Application In Study Of Cholesterol-Lowering Effect Of Dark Tea

Low density lipoprotein receptor is a glycoprotein which is plentiful in cell membranes, and especially it is rich in liver cells. LDLR is closely related to cholesterol metabolism. Most of the cholesterol in blood is cleaned by LDLR attached to the liver cells. Deviant structure and function of LDLR will result in serious diseases such as coronary heart disease, atherosclerosis. Therefore, building up the screening model targeting LDLR is of great significance for searching and discovering new drugs treating hypercholesterolemia.The frontier minorities in China who commonly have high fat diet and drink dark tea, but rarely suffered from fat and hyperlipemia, because dark tea has the effect of regulating hyperlipidemia. The aim of this study is to screen the dark tea varieties which can raise the expression of LDLR. The drugs screening model was built up: Firstly, LDLR promoter was cloned and ligated into luciferase (Luc), then the recombinant plasmid with LDLR/Luc reporter gene was constructed. Secondly, the recombinant plasmid with LDLR/Luc reporter gene and internal reference plamid TK were transfected into HepG2 cells. The simvastatin was chosen as positive control. Various conditions, such as the rate of plamid and positive drug concentration, were optimized. The results showed that the LDLR promoter activity was strongly elevated by simvastatin; its effect was concentration dependent and the Z'factor of this model was 0.72. Which demonstrated that this model was sensitive and stable. Finally, this model was applied to screen 8 kinds of dark tea extracts by water. The results showed that the active effect of Jinhua Tiancheng Tea, Fu Brick Tea, Qin Brick Tea, Pu-erh Tea ripe cake, Liu Pao Tea and Baishaxi Tianjian Tea were stronger, the active value of Jinhua Tiancheng Tea was the highest, which was 1.761. The active effect of Qianliang Tea and Jinjian Tea were lower.