GW1929对于小鼠胆固醇结石的治疗和预防作用及其初步机制研究  

The therapeutic and preventive effects of GW1929 on cholesterol gallstone in mice and Its preliminary mechanism

作　　者：吴凌智 俞聪聪 刘一舟 杨秋萍 Wu Lingzhi

机构地区：[1]嘉兴市第一医院(嘉兴学院附属医院),314000

出　　处：《浙江临床医学》2022年第10期1438-1440,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省嘉兴市科技计划项目(2021AD10023)。

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂GW1929在小鼠胆固醇结石中的治疗作用及其机制。方法通过喂食致石饲料建立小鼠胆固醇结石模型,分组给药8周后,观察胆汁中的胆固醇结晶情况,检测胆汁中胆汁酸(BA)、胆固醇(CH)的浓度,以及血清中高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)的浓度。通过Westernblot方法检测肝脏中羟甲基戊二酸单酰辅酶A还原酶(HMGCR)、胆固醇7α羟化酶(CYP7A1)、小肠中法尼醇受体(FXR)、成纤维生长因子15(FGF15)蛋白表达水平。结果GW1929可抑制FXR和FGF15的表达,提高CYP7A1表达水平,促进胆固醇合成胆汁酸,减少胆固醇结晶的形成。结论GW1929可抑制小鼠胆固醇结石的形成,其机制可能与抑制FXR-FGF15通路以及促进CYP7A1表达有关。Objective To investigate the therapeutic and preventive effects and mechanism of GW1929,which is a novel peroxisome proliferatoractivated receptors gamma(PPARγ)agonist on cholesterol biosynthesis and decomposition in mice.Methods Lithogenic diets was given to mice in order to establish the gallstone model.After 8 weeks of administration,the microscope was used to observe cholesterol crystals in bile.The concentration of bile acid(BA),cholesterol(CH)in bile,and the concentration of high-density lipoprotein cholesterol(HDL-C),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)in serum were detected with commercial kits.The expression of HMGCR and CYP7A1 in liver and FXR and FGF15 in small intestine were detected with western blot.Results GW1929 inhibited the expression of FXR and FGF15 while increased the expression of CYP7A1.Moreover,GW1929 promoted cholesterol to synthesize bile acid and reduced the formation of cholesterol crystal.Conclusion GW1929 can prevent and treat cholesterol stones in mice,and its mechanism may be related to the inhibition of FXR-FGF15 pathway and the promotion of CYP7A1 expression.

关 键 词：胆固醇结石 PPARΓ CYP7A1 FXR FGF15 

分 类 号：R575.62[医药卫生—消化系统]