大黄素诱导LXRα-ABCA1信号通路减少非酒精性脂肪性肝病细胞模型的脂质沉积  

Lipid-lowering Effect of Emodin in a NAFLD Cell Model Through LXRα-ABCA1 Pathway

作　　者：宁巍 杨金连 张涛 NING Wei;YANG Jinlian;ZHANG Tao(Department of Pharmacy,Hunan Provincial People's Hospital the First Affiliated Hospital of Hunan Normal University,Changsha 410005,China;Department of Pharmacy,Guangzhou Women and Children's Medical Center,Guangzhou 510623,China)

机构地区：[1]湖南省人民医院(湖南师范大学附属第一医院)药学部,长沙410005 [2]广州市妇女儿童医疗中心药学部,广州510623

出　　处：《医药导报》2022年第12期1747-1752,共6页Herald of Medicine

基　　金：广东省区域联合基金-青年基金项目(2020A1515110314);广东省医院协会药学科研专项基金(2022YXKY18)。

摘　　要：目的通过体外模型探究大黄素改善肝细胞脂质沉积的作用机制,为大黄素治疗非酒精性脂肪性肝病(NAFLD)提供实验依据。方法使用油酸和棕榈酸构建肝细胞脂肪变性模型,实验分为正常对照组、模型对照组、大黄素组和阿托伐他汀钙(阳性对照)组,油红O染色和尼罗红染色分析细胞的油脂蓄积情况,并测定细胞中三酰甘油(TG)和胆固醇(TC)含量。使用RT-qPCR和Western blotting检测大黄素对LXRα和ABCA1的mRNA和蛋白影响,使用荧光素酶报告基因考察大黄素对LXRα-ABCA1通路的作用,使用RNA干扰实验敲低LXRα考察大黄素通过LXRα-ABCA1通路减少细胞脂质的机制。结果大黄素显著降低了细胞的脂质蓄积,并降低细胞内TG和TC含量(P<0.05)。大黄素增加了LXRα和ABCA1基因以及蛋白表达水平,并提高了LXRα-ABCA1双荧光素酶系统的相对荧光值(P<0.05)。敲低LXRα后,大黄素减少细胞脂质蓄积的作用显著降低。结论大黄素可显著改善体外细胞脂质蓄积,激活LXRα-ABCA1信号通路促进脂质外排可能是大黄素缓解NAFLD的重要机制。Objective Exploring the mechanism of emodin in improving hepatocyte lipid deposition can provide the theoretical basis for treating non-alcoholic fatty liver disease(NAFLD).Methods HepG2 cells were treated with oleic acid and palmitic acid to induce NAFLD cell models.The cells were divided into the normal control group,model control group,emodin group,and atorvastatin(positive)group.Oil red O and Nile red staining were used to analyze cell lipid accumulation.Triglyceride(TG)and total cholesterol(TC)in cells were also measured.RT-qPCR and western blot were used to detect the mRNA and protein levels of LXRαand ABCA1.The luciferase reporter assessed the effect of emodin on the LXRα-ABCA1 pathway.LXRαsiRNA was used to investigate emodin to reduce lipid accumulation through the LXRα-ABCA1 pathway.Results Oil red O staining and Nile Red staining showed that emodin attenuated the lipid accumulation.In addition,emodin treatment decreased the TG and TC levels(P<0.05).Emodin increased LXRαand ABCA1 mRNA and protein expression.The relative fluorescence value of the LXRα-ABCA1 luciferase system was further activated by emodin(P<0.05).The effect of emodin on reducing cell lipid accumulation was significantly reduced after the knockdown of LXRα.Conclusion Emodin significantly reduced lipid accumulation in vitro.Activating the LXRα-ABCA1 pathway to promote lipid effluent may be the underlying mechanism for emodin in alleviating NAFLD.

关 键 词：大黄素 非酒精性脂肪性肝病 LXRα-ABCA1信号通路 HepG2细胞 

分 类 号：R966[医药卫生—药理学]