当飞利肝宁胶囊调控肝脏氧化应激改善非酒精性脂肪性肝病小鼠的机制研究

赵燕婷; 舒祥兵; 杨志新; 李光萍

doi:10.16306/j.1008-861x.2021.05.007

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当飞利肝宁胶囊调控肝脏氧化应激改善非酒精性脂肪性肝病小鼠的机制研究

实验研究 | 更新时间：2022-09-09

- 当飞利肝宁胶囊调控肝脏氧化应激改善非酒精性脂肪性肝病小鼠的机制研究
- Mechanism of Dangfei Liganning Capsule on non-alcoholic fatty liver disease via inhibiting liver oxidative stress in mice
- 上海中医药大学学报 2021年35卷第5期页码：37-43,74
- 作者机构：
  
  1.上海中医药大学附属曙光医院宝山分院，上海市宝山区中西医结合医院（上海　201999）
- 作者简介：
  
  赵燕婷，女，住院医师，在读硕士生，主要从事中医药防治糖脂代谢性疾病的基础与临床研究
  杨志新，副主任医师；E-mail：yangzhixin931018@163.com。李光萍，主管护师；E-mail：124137081@qq.com
- 基金信息：
  
  国家自然科学基金资助项目(81804020)
- DOI：10.16306/j.1008-861x.2021.05.007
  中图分类号：
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赵燕婷, 舒祥兵, 杨志新, 等. 当飞利肝宁胶囊调控肝脏氧化应激改善非酒精性脂肪性肝病小鼠的机制研究[J]. 上海中医药大学学报, 2021,35(5):37-43,74.

ZHAO Yanting, SHU Xiangbing, YANG Zhixin, et al. Mechanism of Dangfei Liganning Capsule on non-alcoholic fatty liver disease via inhibiting liver oxidative stress in mice[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(5):37-43,74.
赵燕婷, 舒祥兵, 杨志新, 等. 当飞利肝宁胶囊调控肝脏氧化应激改善非酒精性脂肪性肝病小鼠的机制研究[J]. 上海中医药大学学报, 2021,35(5):37-43,74. DOI： 10.16306/j.1008-861x.2021.05.007.

ZHAO Yanting, SHU Xiangbing, YANG Zhixin, et al. Mechanism of Dangfei Liganning Capsule on non-alcoholic fatty liver disease via inhibiting liver oxidative stress in mice[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(5):37-43,74. DOI： 10.16306/j.1008-861x.2021.05.007.

摘要

目的：,2,探讨当飞利肝宁胶囊对高脂饮食诱导的非酒精性脂肪性肝病（NAFLD）小鼠的治疗作用及潜在机制。,方法：,2,雄性C57BL/6J小鼠随机分为正常组、模型组和当飞利肝宁（0.42 g·kg,－1,·d,－1,）组，每组10只。除正常组外，其他小鼠给予高脂饲料喂养12周，以诱导模型。造模后，各组小鼠灌胃给予相应药物干预，连续4周。末次给药后，取血清，收集肝组织。生化分析仪检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）水平；油红O染色和HE染色后观察肝组织形态学变化。试剂盒检测肝组织TC、TG、丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）水平；PCR检测肝脏核因子E2相关因子2（,Nrf2,）、细胞色素P450家族成员2E1（,CYP2E1,）、血红素氧合酶1（,HO-1,）、NADPH醌氧化还原酶（,NQO1,）、谷胱甘肽硫转移酶P1（,GSTP1,）的mRNA表达；Western blot检测肝脏Nrf2和CYP2E1的蛋白表达。,结果：,2,①与模型组相比，当飞利肝宁组小鼠血清ALT、AST、TC和LDL水平显著降低（,P,<,0.05）。②当飞利肝宁胶囊能明显降低模型小鼠的肝脏TG水平（,P,<,0.05），且明显减轻模型小鼠肝组织肝细胞脂肪变性、脂质堆积；与模型组相比，当飞利肝宁组小鼠肝脏SOD活性明显升高（,P,<,0.05），MDA含量显著降低（,P,<,0.05）。③模型组小鼠肝脏,Nrf2,、,HO-1,、,GSTP1,、,NQO1,及,CYP2E1,的mRNA表达水平较正常组均显著下降（,P,<,0.05，,P,<,0.01），当飞利肝宁胶囊干预可明显上调模型小鼠肝脏,Nrf2,、,GSTP1,及,NQO1,的mRNA表达水平（,P,<,0.05）。④模型组小鼠肝脏Nrf2和CYP2E1的蛋白表达水平较正常组明显降低（,P,<,0.05，,P,<,0.01），当飞利肝宁胶囊干预可明显升高模型小鼠肝脏Nrf2和CYP2E1的蛋白表达水平（,P,<,0.05）。,结论：,2,当飞利肝宁胶囊对高脂饮食诱导的NAFLD小鼠具有良好的治疗作用，其作用机制与降低Nrf2介导的肝脏氧化应激水平有关。

Abstract

Objective:,2,To investigate the therapeutic effects and potential mechanisms of Dangfei Liganning Capsule on high fat diet induced non-alcoholic fatty liver disease(NAFLD) in mice.,Methods:,2,Male C57BL/6J mice were randomly divided into the normal group, model group and Dangfei Liganning(0.42 g·kg,-1,·d,-1,) group, 10 mice in each group.Except the normal group, mice in the other groups were fed with high fat diet for 12 weeks to induce the model.After modeling, each group was treated with the corresponding drug by intragastric administration for 4 weeks.After the last administration, the serum was taken and the liver tissue was collected.The serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL) and high-density lipoprotein(HDL) were detected by biochemical analyzer.The morphological changes of liver tissue were observed after oil red O staining and HE staining.The levels of TC, TG, malondialdehyde(MDA), glutathione(GSH) and superoxide dismutase(SOD) in liver tissue were detected by kits.The mRNA expressions of nuclear factor erythroid 2-related factor 2(,Nrf2,), cytochrome P450 2E1(,CYP2E1,), heme oxygenase 1(,HO-1,), NADPH quinone oxidoreductase 1(,NQO1,) and glutathione S-transferase P1(,GSTP1,) in liver tissue were detected by PCR.The protein expressions of Nrf2 and CYP2E1 in liver tissue were detected by Western blot.,Results:,2,①Compared with the model group, the serum levels of ALT, AST, TC and LDL were significantly decreased in the Dangfei Liganning group(,P,<,0.05) .②Dangfei Liganning Capsule could significantly reduce the TG level in the liver of model mice(,P,<,0.05), and significantly alleviate the hepatocyte steatosis and lipid accumulation in the model mice.Compared with the model group, the activity of SOD in the liver was increased obviously in the Dangfei Liganning group(,P,<,0.05), and the content of MDA in the liver was significantly decreased(,P,<,0.05) .③The mRNA expression levels of ,Nrf2,HO-1,GSTP1,NQO1, and ,CYP2E1, in the model group were significantly lower than those in the normal group(,P,<,0.05,P,<,0.01) .Dangfei Liganning Capsule could significantly up-regulate the mRNA expression levels of ,Nrf2,GSTP1, and ,NQO1, in the liver of model mice(,P,<,0.05) .④The protein expression levels of Nrf2 and CYP2E1 in the model group were significantly lower than those in the normal group(,P,<,0.05,P,<,0.01) .Dangfei Liganning Capsule could significantly increase the protein expression levels of Nrf2 and CYP2E1 in the liver of model mice(,P,<,0.05) .,Conclusion:,2,Dangfei Liganning Capsule shows good therapeutic effects on NAFLD mice induced by high fat diet, and its mechanism is related to the decrease of Nrf2 mediated oxidative stress in liver.

关键词

当飞利肝宁胶囊非酒精性脂肪性肝病氧化应激核因子E2相关因子2小鼠

Keywords

Dangfei Liganning CapsuleNAFLDoxidative stressNrf2mouse

references

张韬，张丽娟，韩丹. 当飞利肝宁胶囊联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的临床研究[J]. 现代药物与临床，2019，34(5)： 1402-1405.

武敬，彭雁忠. 当飞利肝宁胶囊治疗非酒精性单纯性脂肪肝的效果[J]. 实用临床医学，2018，19(6)： 12-14.

宋寿龙，徐湘江，张建设，等. 当飞利肝宁胶囊联合阿托伐他汀钙片治疗非酒精性脂肪性肝病临床观察[J]. 河北中医，2018，40(7)： 92-95.

宋海燕，刘洋，毛志敏，等. 当飞利肝宁胶囊预防非酒精性脂肪性肝病大鼠肝纤维化[J]. 中西医结合肝病杂志，2013，23(3)： 154-156.

刘翎，谢贤春，吉中和，等. 当飞利肝宁治疗实验性脂肪肝的研究[J]. 中国中药杂志，2003，28(8)： 787-789.

DAY C P，JAMES O F. Steatohepatitis： A tale of two “Hits”？ [J]. Gastroenterology，1998，114(4)： 842-845.

赵灏，陈伟平，蒋兰英. 当飞利肝宁胶囊对慢性乙型肝炎患者抗氧化体系的影响[J]. 中医杂志，2007，48(5)： 466-466.

MURAG S，AHMED A，KIM D. Recent Epidemiology of Nonalcoholic Fatty Liver Disease[J]. Gut Liver，2021，15(2)： 206-216.

MAKRI E，GOULAS A，POLYZOS S A. Epidemiology，Pathogenesis，Diagnosis and Emerging Treatment of Nonalcoholic Fatty Liver Disease[J]. Arch Med Res，2021，52(1)： 25-37.

NYAKUDYA T T，MUKWEVHO E，NKOMOZEPI P，et al. Neonatal intake of oleanolic acid attenuates the subsequent development of high fructose diet-induced non-alcoholic fatty liver disease in rats[J]. J Dev Orig Health Dis，2018，9(5)： 500-510.

武俊紫，杨斌，宋波，等. 龙胆苦苷对非酒精性脂肪肝病大鼠AMPK信号通路的调节作用[J]. 中草药，2018，49(21)： 197-203.

刘芳，谢贤春，吉中和，等. 当飞利肝宁胶囊治疗高脂血症及脂肪肝的实验研究[J]. 医学理论与实践，2007，20(3)： 251-252.

ČOLAK E，PAP D. The role of oxidative stress in the development of obesity and obesity-related metabolic disorders[J]. J Med Biochem，2021，40(1)： 1-9.

CHEN Z，TIAN R F，SHE Z G，et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med，2020，152： 116-141.

LI J D，WANG T Q，LIU P P，et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD[J]. Food Funct，2021，12(9)： 3898-3918.

ALFARIS N A，ALSHAMMARI G M，ALTAMIMI J Z，et al. The protective effect of shrimp cooked in different methods on high-cholesterol-induced fatty liver in rats[J]. Saudi J Biol Sci，2021，28(1)： 170-182.

XU Y，KE H H，LI Y T，et al. Malvidin-3-O-Glucoside from Blueberry Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Transcription Factor EB-Mediated Lysosomal Function and Activating the Nrf2/ARE Signaling Pathway[J]. J Agric Food Chem，2021，69(16)： 4663-4673.

HAN X，DING C H，ZHANG G D，et al. Liraglutide ameliorates obesity-related nonalcoholic fatty liver disease by regulating Sestrin2-mediated Nrf2/HO-1 pathway[J]. Biochem Biophys Res Commun，2020，525(4)： 895-901.

SHEN B Y，FENG H H，CHENG J Q，et al. Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signaling pathways [J]. J Cell Mol Med，2020，24(9)： 5097-5108.

XIA S F，SHAO J，ZHAO S Y，et al. Niga-ichigoside F1 ameliorates high-fat diet-induced hepatic steatosis in male mice by Nrf2 activation[J]. Food Funct，2018，9(2)： 906-916.

LIU Z X，DOU W J，NI Z，et al. Deletion of Nrf2 leads to hepatic insulin resistance via the activation of NF-κB in mice fed a high-fat diet[J]. Mol Med Rep，2016，14(2)： 1323-1331.

MEAKIN P J，CHOWDHRY S，SHARMA R S，et al. Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress，perturbation of the unfolded protein response，and disturbance in the expression of metabolic enzymes but not with insulin resistance [J]. Mol Cell Biol，2014，34(17)： 3305-3320.

OU Q，WENG Y Y，WANG S W，et al. Silybin Alleviates Hepatic Steatosis and Fibrosis in NASH Mice by Inhibiting Oxidative Stress and Involvement with the Nf-κB Pathway[J]. Dig Dis Sci，2018，63(12)： 3398-3408.

NI X J，WANG H Y. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease （NAFLD）[J]. Am J Transl Res，2016，8(2)： 1073-1081.

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