Effect of Shenge Recipe on oxidative stress and mitochondrial function of steatosis hepatocytes

ZHENG Yanxi; YU Zhuo; FANG Miao; GAO Yating; GAO Yueqiu

doi:10.16305/j.1007-1334.2023.2112078

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Effect of Shenge Recipe on oxidative stress and mitochondrial function of steatosis hepatocytes

更新时间：2023-02-24

- Effect of Shenge Recipe on oxidative stress and mitochondrial function of steatosis hepatocytes
- Shanghai Journal of Traditional Chinese Medicine Vol. 57, Issue 2, Pages: 51-58(2023)
- 作者机构：
  
  1.上海中医药大学附属曙光医院肝病科（上海 201203）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2023.2112078
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郑彦希,余卓,方淼,等.参葛方对脂肪变性肝细胞氧化应激和线粒体功能的影响[J].上海中医药杂志,2023,57(2):51-58.

ZHENG Yanxi,YU Zhuo,FANG Miao,et al.Effect of Shenge Recipe on oxidative stress and mitochondrial function of steatosis hepatocytes[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):51-58.
郑彦希,余卓,方淼,等.参葛方对脂肪变性肝细胞氧化应激和线粒体功能的影响[J].上海中医药杂志,2023,57(2):51-58. DOI： 10.16305/j.1007-1334.2023.2112078.

ZHENG Yanxi,YU Zhuo,FANG Miao,et al.Effect of Shenge Recipe on oxidative stress and mitochondrial function of steatosis hepatocytes[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):51-58. DOI： 10.16305/j.1007-1334.2023.2112078.

摘要

目的,2,探讨参葛方抑制脂肪变性肝细胞氧化应激和线粒体功能的相关机制。,方法,2,①将30只雄性C57BL/6J小鼠分为正常组、模型组、参葛方治疗组（给药剂量15.75 g·kg,-1,·d,-1,），每组10只，通过蛋氨酸和胆碱缺乏（MCD）饮食诱导脂肪肝模型，连续16周。参葛方治疗组于第13周行中药灌胃至结束，观察小鼠肝组织炎症、脂质沉积、过氧化水平。②体外使用0.2 mmol/L棕榈酸作用于人肝癌细胞（HepG2细胞）24 h诱导脂肪变性模型，结合沉默信息调节蛋白3（SIRT3）抑制剂（3-TYP）、腺苷酸活化蛋白激酶（AMPK）抑制剂（Compound C）、参葛方药物血清、正常大鼠血清处理，分为对照组（Control）、模型组（PA）、参葛方组（PA+SGF）、SIRT3抑制组（PA+3-TYP）、AMPK抑制组（PA+ Compound C）、参葛方+SIRT3抑制组（PA+3-TYP+SGF）、参葛方+AMPK抑制组（PA+ Compound C +SGF）。观察氧化应激水平［细胞活性氧（ROS）、丙二醛（MDA）］、线粒体功能［腺苷三磷酸（ATP）］等指标及其对SIRT3、p-AMPK/AMPK、氧化物酶体增殖活化受体γ共激活因子-1α（PGC-1α）含量的影响，电镜下观察线粒体结构。,结果,2,①与PA小鼠比较，PA+SGF脂质沉积、过氧化水平均降低。②与PA比较，PA+SGF的三酰甘油（TG）、肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）水平降低（,P,<,0.05），ROS、MDA水平降低（,P,<,0.01），PGC-1α、ATP生成量增加（,P,<,0.05），电镜下线粒体损伤减轻。而使用3-TYP和Compound C处理后以上作用均减弱。,结论,2,参葛方可抑制氧化应激损伤、改善线粒体功能、减轻肝细胞脂肪变性，其作用机制可能与上调SIRT3、AMPK表达有关。

Abstract

Objective,2,To explore the mechanism of Shenge Recipe on inhibiting oxidative stress and mitochondrial function of steatosis hepatocytes.,Methods,2,①Thirty male C57BL/6J mice were divided into normal group， model group and Shenge Recipe group （the dosage of 15.75 g·kg,-1,·d,-1,）， with 10 mice in each group. The fatty liver model was induced by methionine and choline deficiency （MCD） diet for 16 weeks， while the mice in the Shenge Recipe group was given intragastric administration of traditional Chinese medicine since the 13th week. The levels of liver inflammation， lipid deposition and peroxidation were observed. ②Human hepatoma cells （HepG2 cells） were pretreated with palmitic acid （PA，0.2 mmol/L） for 24 h to induce hepatic steatosis model. Then the cells were treated with silencing information regulatory protein 3 （SIRT3） inhibitor （3-TYP）， adenylate activated protein kinase （AMPK） inhibitor （Compound C）， Shenge Recipe drug serum and normal mouse serum and were divided into 7 groups： Control group （Control）， model group （PA）， Shenge Recipe group （PA+SGF）， SIRT3 inhibition group （PA+3-TYP）， AMPK inhibition group （PA+CMC）， Shenge Recipe+SIRT3 inhibition group （PA+3-TYP+SGF） and Shenge Recipe+AMPK inhibition group （PA+CMC+SGF）. The levels of oxidative stress including cellular reactive oxygen species （ROS）， malondialdehyde（MDA）， mitochondrial function including adenosine triphosphate （ATP） and their effects on the contents of SIRT3， p-AMPK/AMPK and oxisome proliferator activated receptor γ coactivator-1α （PGC-1α） were observed. The structure of mitochondria was observed under electron microscope.,Results,2,①Compared with PA， the levels of lipid deposition and peroxide in PA+SGF were all reduced. ②Compared with PA group， the levels of TG， TNF-α and IL-6 in PA+SGF group were decreased significantly （,P,<,0.05）. And the levels of ROS and MDA were decreased as well（,P,<,0.01）， while PGC-1α and ATP levels showed the increase in PA+SGF group （,P,<,0.05）. The damage of mitochondria was alleviated under electron microscope. However， the above effects were weakened after treatment with 3-TYP and Compound C.,Conclusion,2,Shenge Recipe can inhibit oxidative stress injury， improve mitochondrial function and reduce hepatocyte steatosis， and its mechanism may be related to up-regulating the expression of SIRT3 and AMPK.

关键词

非酒精性脂肪性肝炎代谢相关脂肪性肝病参葛方氧化应激线粒体小鼠模型中药研究

Keywords

nonalcoholic steatohepatitismetabolic associated fatty liver diseaseShenge Recipeoxidative stressmitochondriamouse modeltraditional Chinese herbal medicine research

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