HMGCR对脂肪肝奶牛肝脏胆汁酸及脂质代谢机制
Mechanism of HMGCR on liver bile acid and lipid metabolism in dairy cow with fatty liver
高畅鸿 1王爽 1田艳 1范文文 1李杰 1杨威1
作者信息
- 1. 黑龙江八一农垦大学动物科技学院,黑龙江大庆 163319
- 折叠
摘要
为了研究3羟基3甲基戊二酰辅酶A还原酶(HMGCR)对脂肪肝奶牛肝脏胆汁酸(BAs)及脂质代谢机制,本研究通过分离原代犊牛肝细胞并利用高浓度非酯化脂肪酸(NEFA)处理体外构建肝脂蓄积模型,然后加入HMGCR过表达腺病毒(Ad-HMGCR)及过表达腺病毒对照(Ad-GFP).利用试剂盒检测了肝细胞甘油三酯(TAG),脂滴荧光检测脂滴变化,及实时荧光定量PCR检测BAs合成和脂肪酸合成及氧化因子变化.结果显示,与Ad-GFP+NEFA组相比,Ad-HMGCR+NEFA组的TAG含量及脂滴荧光显著减少.实时荧光定量PCR结果显示,Ad-HMGCR+NEFA组肝细胞BAs合成因子CYP7A1、CYP8B1、CYP7B1和CYP27A1,BAs转运因子ABCC2和ABCB11及脂肪酸合成因子ACC1、FAS和SREBP1C显著低于Ad-GFP+NEFA组;Ad-H MGCR+NEFA组调控肝细胞BAs合成因子FXR及脂氧化因子CPT1A的水平高于Ad-GFP+NEFA组.结果表明,HMGCR 过表达可显著减轻脂肪肝奶牛肝脏BAs和脂滴蓄积.
Abstract
In order to investigate the mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)on liver bile acid(BAs)and lipid metabolism of dairy cows with fatty liver,A liver lip-id accumulation model was established by isolating primary calf hepatocytes and treating them with high concentration of non-esterified fatty acids(NEFA)in vitro.Then,HMGCR overex-pressed adenovirus(Ad-HMGCR)and overexpressed adenovirus control(Ad-GFP)were added.Hepatocyte triglyceride(TAG)was detected by the kit,lipid droplet changes were detected by lip-id droplet fluorescence,and BAs synthesis,fatty acid synthesis and oxidation factor changes were detected by real-time fluorescence quantitative PCR.The results showed that TAG content and lip-id droplet fluorescence were significantly reduced in Ad-HMGCR+NEFA group compared with Ad-GFP+NEFA group.Real-time fluorescence quantitative PCR results showed that CYP7A1,CYP8B1,CYP7B1 and CYP27A1 of hepatocyte BAs synthesis factors in Ad-HMGCR+NEFA group,BAs transporters ABCC2 and ABCB11 and fatty acid synthesis factors ACC1,FAS and SREBP1C were significantly lower than those in Ad-GFP+NEFA group.The levels of BAs syn-thesis factor FXR and lipid oxidation factor CPT1A in Ad-HMGCR+NEFA group were higher than those in Ad-GFP+NEFA group.The results showed that overexpression of HMGCR could significantly reduce BAs and lipid accumulation in the liver of dairy cows with fatty liver.
关键词
奶牛/脂肪肝/胆汁酸/胆固醇/HMGCRKey words
dairy cow/fatty liver/bile acids/cholesterol/HMGCR引用本文复制引用
出版年
2024
NETL
NSTL
万方数据