广西医科大学学报2020，Vol.37Issue(3)：347-355,9.DOI:10.16190/j.cnki.45-1211/r.2020.03.001
SIRT1过表达介导PPARγ-PGC1α-NRF2通路对肥胖症大鼠肝脏脂肪沉积和变性及氧化应激的调节作用
SIRT1 overexpression mediates the regulation of hepatic lipid accumulation, fatty degeneration and oxidative stress of liver through the PPAR γ-PGC1α-NRF2 pathway in obese rats
摘要
Abstract
Objective: To investigate the effect of silent information regulator 1 (SIRT1) overexpression on hepatic lipid accumulation,fatty degeneration,and oxidative stress of liver in obese rats by mediating the PPARγ-PGC1α-NRF2 pathway.Methods: After constructing the SIRT1 lentiviral vector (LV),the rats were divided into control group,obesity model group,obesity + LV group,and obesity + LV + SIRT1 overexpression (obesity + LV-SIRT1) group using a random number table.The nose-anus length was measured by a tape measure and the Lee's index was calculated;blood glucose level was measured by a Roche blood glucose meter;total cholesterol (TC),triglycerides (TG),low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C) levels were measured by a chemistry analyzer;hematoxylin-eosin staining (HE) and oil red O were used to detect hepatic lipid accumulation and fatty degeneration of liver;enzyme-linked immunosorbent assay (ELISA) was used to detect superoxide dismutase (SOD),lactate dehydrogenase (LDH),malondialdehyde (MDA) and reactive oxygen species (ROS);reverse transcription-polymerase chain reaction (RT-PCR) was used to detect peroxisome proliferator-activated receptor γ (PPARγ),peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α),and nuclear factor-E2-related factor-2 (Nrf2) mRNA levels;Western blot was used to detect SIRTI,PPARγ,PGC-1α,and Nrf2 protein expression levels.Results: Compared with the obesity model group,the results of the study showed that SIRT1 protein level was significantly increased (P＜0.05);Lee's index,body weight,and blood glucose levels were significantly reduced (P＜0.05);TC,TG,and LDL were significantly reduced (P＜0.05);HDL content was significantly increased (P＜0.05);lipid accumulation and fatty degeneration were significantly alleviated;MDA,ROS,and LDH were significantly reduced (P＜0.05);SOD was significantly increased (P＜0.05);PPARγ,PGClα,Nrf2 mRNA and protein levels were significantly increased (P ＜0.05) in the obesity + LV-SIRT1 group.Conclusion: SIRT1 overexpression may mediate the regulation of hepatic lipid accumulation,fatty degeneration,and oxidative stress of the liver in obese rats through the PPARγ-PGC1α-NRF2 pathway.关键词
肥胖症/沉默信息调节因子1/氧化应激/PPARγ-PGC1α-NRF2通路Key words
obesity/silent information regulator 1/oxidative stress/PPARγ-PGC1α-NRF2 pathway分类
医药卫生引用本文复制引用
兰天,刘巍梦,邹阳,邱平..SIRT1过表达介导PPARγ-PGC1α-NRF2通路对肥胖症大鼠肝脏脂肪沉积和变性及氧化应激的调节作用[J].广西医科大学学报,2020,37(3):347-355,9.基金项目
This study was supported by a grant from the Education Department of Sichuan Province (No.18Z065). （No.18Z065）
