基于SIRT3/FXO1信号通路探讨大黄素对NASH大鼠肝细胞损伤和肝组织炎症的影响

肝脏 ›› 2019, Vol. 24 ›› Issue (5): 510-514.

基于SIRT3/FXO1信号通路探讨大黄素对NASH大鼠肝细胞损伤和肝组织炎症的影响

寇小妮, 解新科, 郝明霞, 吴维, 边倩, 马文军

712000 咸阳陕西中医药大学附属医院肝病二科

收稿日期:2018-12-29 发布日期:2020-04-10
基金资助:
陕西省科技厅社会发展领域项目(2018SF295)

Effects of Emodin on Hepatocyte Injury and Hepatic Inflammation in NASH Rats Based on SIRT3/FXO1 Signaling Pathway

KOU Xiao-ni, XIE Xing-ke, HAO Ming-xia, WU Wei, BIAN Qian, MA Wen-jun

Second Division of Hepatology, Affiliated Hospital University of Traditional Chinese Medicine, Xianyang, 712000, China

Received:2018-12-29 Published:2020-04-10

摘要/Abstract

摘要： 目的基于SIRT3/FXO1信号通路探讨大黄素对非酒精性脂肪性肝炎(NASH)大鼠细胞损伤和肝组织炎症的影响。方法 SD大鼠100只,随机分成5组:对照组、模型组、大黄素低、中、高剂量组。对照组给予普通饲料,模型组和大黄素组给予高脂饮食构建NASH模型。造模成功后,大黄素组分别给予10、20、40 mg/kg大黄素灌胃。评估肝脏脂肪变性,炎症反应和球状样变化及 NASH 活动度积分(NAS),检测各组大鼠肝组织AST、ALT、TNF-α、IL-6、SIRT3、FXO1 mRNA、蛋白水平以及CASPASE-3、CASPASE-6、CASPASE-9水平。结果与对照组比较,大黄素各剂量组脂肪变积分、炎症坏死灶积分、气球样变积分、NAS 积分、AST、ALT、TNF-α、IL-6、CASPASE-3、CASPASE-6、CASPASE-9水平升高,SIRT3、FXO1 mRNA、蛋白表达水平降低(P<0.05);与模型组比较,大黄素各剂量组脂肪变积分、炎症坏死灶积分、气球样变积分、NAS 积分、AST、ALT、TNF-α、IL-6、CASPASE-3、CASPASE-6、CASPASE-9水平降低,SIRT3、FXO1 mRNA、蛋白表达水平升高,且随着大黄素各剂量组给药剂量的增加,脂肪变积分、炎症坏死灶积分、气球样变积分、NAS 积分、AST、ALT、TNF-α、IL-6、CASPASE-3、CASPASE-6、CASPASE-9水平逐渐降低,SIRT3、FXO1 mRNA、蛋白表达水平逐渐升高,剂量-效应关系明显(P<0.05)。结论大黄素能促进SIRT3、FXO1 mRNA、蛋白的表达,降低肝脏细胞炎性反应,减少肝细胞凋亡,进而减轻NASH大鼠肝细胞损伤程度。

关键词: 大黄素, 非酒精性脂肪性肝炎, SIRT3/FXO1信号通路

Abstract: Objective To investigate the effects of emodin on hepatocyte injury and hepatic inflammation in non-alcoholic steatohepatitis (NASH) rats based on Sirtuin 3 (SIRT3)/forkhead box O1 (FOXO1) signaling pathway.Methods A total of 100 Sprague-Dawley rats were randomly divided into 5 groups, including control group, model group, low-, medium- and high-dose emodin groups. NASH models were established by feeding high-fat diets for 12 weeks. And then 3 emodin groups received the corresponding treatments, while the control group and model group were given the same volume of normal saline. At the end of the experiment, hepatic steatosis, inflammation, ballooning degeneration and nonalcoholic fatty liver disease activity score (NAS) were evaluated, and many other indexes were detected, including levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), messenger ribonucleic acid, expression of SIRT3, FOXO1, caspase-3, caspase-6, and caspase-9 in rat liver tissues.Results The scores of steatosis, inflammation and ballooning degeneration, NAS, levels of AST, ALT, TNF-α, IL-6, caspase-3, caspase-6, and caspase-9 in 3 emodin groups were lower than those in model group. With the increase of the dosage of emodin in each dose group, the scores and levels gradually decreased. While the mRNA and protein levels of SIRT3 and FOXO1 in 3 emodin groups were higher than those in model group. The higher dose emodin the rats had received, the higher the expression levels of SIRT3 and FOXO1 became. Furtheremore, all the parameters changed in a dose-dependent manner (P<0.05).Conclusion Emodin reduce the hepatic inflammation and hepatocyte apoptosis, and alleviate hepatocytes injury in NASH rats through increasing the expression of SIRT3 and FOXO1.

Key words: Emodin, Non-alcoholic steatohepatitis, Sirtuin 3/forkhead box O1 signaling pathway

寇小妮, 解新科, 郝明霞, 吴维, 边倩, 马文军. 基于SIRT3/FXO1信号通路探讨大黄素对NASH大鼠肝细胞损伤和肝组织炎症的影响[J]. 肝脏, 2019, 24(5): 510-514.

KOU Xiao-ni, XIE Xing-ke, HAO Ming-xia, WU Wei, BIAN Qian, MA Wen-jun. Effects of Emodin on Hepatocyte Injury and Hepatic Inflammation in NASH Rats Based on SIRT3/FXO1 Signaling Pathway[J]. Chinese Hepatolgy, 2019, 24(5): 510-514.