[1]石丹丹,艾碧琛,李木兰,等.基于FXR/SHP/PEPCK和FXR/ApoCⅡ通路探讨茵陈五苓散对代谢相关脂肪性肝病大鼠糖脂代谢的作用[J].陕西中医,2025,46(2):153-158.[doi:DOI:10.3969/j.issn.1000-7369.2025.02.002]
　SHI Dandan,AI Bichen,LI Mulan,et al.Effects of Yinchen Wuling powder on glycolipid metabolism in metabolic associated fatty liver disease rats based on FXR/SHP/PEPCK and FXR/ApoCⅡ pathways[J].,2025,46(2):153-158.[doi:DOI:10.3969/j.issn.1000-7369.2025.02.002]
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基于FXR/SHP/PEPCK和FXR/ApoCⅡ通路探讨茵陈五苓散对代谢相关脂肪性肝病大鼠糖脂代谢的作用
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年2期
页码:
153-158
栏目:
基础研究
出版日期:
2025-02-05

文章信息/Info

Title:
Effects of Yinchen Wuling powder on glycolipid metabolism in metabolic associated fatty liver disease rats based on FXR/SHP/PEPCK and FXR/ApoCⅡ pathways
作者:
石丹丹; 艾碧琛; 李木兰; 张 毅; 刘 杰
(湖南中医药大学,湖南 长沙 410208)
Author(s):
SHI Dandan; AI Bichen; LI Mulan; ZHANG Yi; LIU Jie
(Hunan University of Chinese Medicine,Changsha 410208,China)
关键词:
代谢相关脂肪性肝病;  茵陈五苓散;  糖代谢;  脂代谢;  法尼醇X受体;  通路
Keywords:
Metabolic associated fatty liver disease;  Yinchen Wuling powder;  Glucose metabolism;  Lipid metabolism;  Farnesoid X receptor;  Pathway
分类号:
R 575.5
DOI:
DOI:10.3969/j.issn.1000-7369.2025.02.002
文献标志码:
A
摘要:
目的:基于法尼醇X受体(FXR)/微小异源二聚体(SHP)/磷酸烯醇式丙酮酸羧激酶(PEPCK)和FXR/载脂蛋白CⅡ(ApoCⅡ)通路探讨茵陈五苓散对代谢相关脂肪性肝病(MAFLD)大鼠糖脂代谢的作用。方法:用高脂饮食建立MAFLD大鼠模型,将成模大鼠随机分为模型组、茵陈五苓散高剂量组、茵陈五苓散低剂量组和辛伐他汀组,并选取同批次未进行造模处理的大鼠作为空白组。各组给予相应药物和0.9%氯化钠溶液干预4周。灌胃期间每周定时检测各组大鼠的体重和空腹血糖(FBG); 生化法检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST )水平; ELISA法检测胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR); HE染色进行肝脏组织病理学观察; RT-qPCR法检测肝脏FXR、SHP、PEPCK、ApoCⅡ mRNA水平。结果:与模型组比较,茵陈五苓散高剂量组、茵陈五苓散低剂量组和辛伐他汀组体重、肝重和肝指数明显降低(P<0.05); FBG、FINS和HOMA-IR水平明显降低(P<0.05); 血清TG、TC、LDL-C、AST、ALT含量明显降低,HDL-C含量升高(P<0.01); 肝组织结构均有不同程度的改善(P<0.01); FXR、SHP、ApoCⅡ mRNA表达增加(P<0.01),PEPCK mRNA表达减少(P<0.01)。结论:茵陈五苓散能够改善MAFLD大鼠糖脂代谢紊乱和肝脏组织病理状态,其机制可能与调节FXR/SHP/PEPCK和FXR/ApoCⅡ通路有关。
Abstract:
Objective:To explore the effects of Yinchen Wuling powder on glycolipid metabolism in rats with metabolism-associated fatty liver disease(MAFLD)based on the farnesol X receptor(FXR)/small heterodimer protein(SHP)/phosphoenolpyruvate carboxykinase(PEPCK)and FXR/apolipoprotein C Ⅱ(ApoC Ⅱ)pathways.Methods:The MAFLD rat model was established with high-fat diet,and the rats with successful modeling were randomly divided into the model group,Yinchen Wuling powder high-dose group,Yinchen Wuling powder low-dose group and simvastatin group,and the same batch of non-modeling rats were selected as the blank group.Each group was given the corresponding drugs and saline intervention for 4 weeks.During the gavage period,the body mass and fasting blood glucose(FBG)of the rats in each group were measured regularly every week; the biochemical methods were used to determine the levels of total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT)and aspartate transaminase function(AST); ELISA to detect fasting serum lisulin(FINS)levels and calculate Homeostatic Model Assessment for Insulin Resistance(HOMA-IR); HE staining for histopathological observation of the liver; RT-qPCR to detect hepatic FXR,SHP,PEPCK,and ApoCⅡ mRNA levels.Results:Compared with the model group,the body weight,liver weight and liver index were significantly reduced in the Yinchen Wuling powder high-dose group,Yinchen Wuling powder low-dose group and simvastatin group(P<0.05); FBG,FINS and HOMA-IR levels were significantly reduced(P<0.05); serum TG,TC,LDL-C,AST and ALT levels were significantly decreased,and HDL-C levels were increased(P<0.01); liver tissue structure was improved to varying degrees(P<0.01); FXR,SHP,ApoCⅡ mRNA expression increased(P<0.01),PEPCK mRNA expression decreased(P<0.01).Conclusion:Yinchen Wuling powder was able to ameliorate the disorders of glucose-lipid metabolism and liver histopathology in MAFLD rats,and its mechanism may be related to the regulation of FXR/SHP/PEPCK and FXR/ApoCⅡ pathways.

参考文献/References:

[1] ZENG J,FAN J G.From NAFLD to MAFLD:Not just a change in the name[J].Hepatob Pancreat Dis,2022,21(6):511-513.
[2] SANGRO P,DE LA TORRE A M,SANGRO B,et al.Metabolic dysfunction-associated fatty liver disease(MAFLD):An update of the recent advances in pharmacological treatment[J].J Physiol Biochem,2023,79(4):869-879.
[3] RIAZI K,AZHARI H,CHARETTE J H,et al.The prevalence and incidence of NAFLD worldwide:A systematic review and meta-analysis[J].Lancet Gastroenterol,2022,7(9):851-861.
[4] MAN S,DENG Y,MA Y,et al.Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations:A nationwide study with 5.7 million adults in China[J].Gastroenterology,2023,165(4):1025-1040.
[5] 罗艺,周晓玲,刘琳,等.非酒精性脂肪性肝病中医治疗研究进展[J].陕西中医,2024,45(6):859-862.
[6] 郑文博,赵瑛.冬凌草甲素对高脂饮食诱导幼龄大鼠非酒精性脂肪肝的作用及相关机制[J].陕西医学杂志,2021,50(12):1496-1500.
[7] 阳航.茵陈五苓散治疗非酒精性脂肪肝的临床研究[J].中外医学研究,2015,13(5):39-40.
[8] 谭婷,何栋,朱红梅,等.茵陈五苓散对非酒精性脂肪性肝病模型大鼠RBP4的影响[J].中医学报,2020,35(2):344-347.
[9] ADORINI L,TRAUNER M.FXR agonists in NASH treatment[J].J Hepatol,2023,79(5):1317-1331.
[10] 赵然,赵文廷,卢秉久,等.祛湿活血法防治代谢相关脂肪性肝病机制及研究进展[J].河北中医,2023,45(3):514-518.
[11] 延华,柴春艳,张丹,等.基于JNK信号通路探讨自噬、胰岛素抵抗在非酒精性脂肪性肝病中的发病机制[J].陕西医学杂志,2023,52(11):1506-1510.
[12] 汪倩倩.匹伐他汀联合二甲双胍对非酒精性脂肪性肝病患者血脂和肝功能的影响[J].保健医学研究与实践,2023,20(4):17-20.
[13] 南忱.三酰甘油与高密度脂蛋白胆固醇比值联合γ-谷氨酰转肽酶对非酒精性脂肪性肝病的预测价值[J].河北医药,2023,45(3):385-387,391.
[14] ESLAM M,NEWSOME P N,SARIN S K,et al.A new definition for metabolic dysfunction-associated fatty liver disease:An international expert consensus statement[J].J Hepatol,2020,73(1):202-209.
[15] 何聪,孔婧,王慧超,等.祛湿化瘀法治疗非酒精性脂肪肝研究进展[J].陕西中医,2020,41(12):1843-1845.
[16] 闫雅婕,王亚亚,梁轩,等.茵陈化学成分、药理作用及在肝胆疾病中的临床应用研究进展[J].中华中医药学刊,2024,42(11):237-248.
[17] 姜悦航,张越,王妍妍,等.茯苓多糖提取物调控CYP2E1及NF-κB炎症通路改善小鼠酒精性肝病[J].中国中药杂志,2022,47(1):134-140.
[18] HO C,GAO Y,ZHENG D,et al.Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway[J].J Cell Mol Med,2019,23(8):5108-5118.
[19] LIU J,ZHANG Q,LI R L,et al.The traditional uses,phytochemistry,pharmacology and toxicology of Cinnamomi ramulus:A review[J].J Pharm Pharmacol,2020,72(3):319-342.
[20] 曹玉清,郭旸,尚希钰,等.桂枝-泽泻治疗外感疾病中医认识及现代药学研究进展[J].中国实验方剂学杂志,2024,30(24):279-288.
[21] 苏祖清,曾科学,孙朝跃,等.白术挥发油对代谢综合征大鼠糖脂代谢的影响[J].亚太传统医药,2018,14(10):4-7.
[22] JIANG L,ZHANG H,XIAO D,et al.Farnesoid X receptor(FXR):Structures and ligands[J].Comput Struct Biotechnol J,2021,19:2148-2159.
[23] MA K,SAHA P K,CHAN L,et al.Farnesoid X receptor is essential for normal glucose homeostasis[J].J Clin Invest,2006,116(4):1102-1109.
[24] YAMAGATA K,DAITOKU H,SHIMAMOTO Y,et al.Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1[J].J Biol Chem,2004,279(22):23158-23165.
[25] KAST H R,NGUYEN C M,SINAL C J,et al.Farnesoid X-activated receptor induces apolipoprotein C-Ⅱ transcription:A molecular mechanism linking plasma triglyceride levels to bile acids[J].Mol Endocrinol,2001,15(10):1720-1728.
[26] GHOSH LASKAR M,ERIKSSON M,RUDLING M,et al.Treatment with the natural FXR agonist chenodeoxycholic acid reduces clearance of plasma LDL whilst decreasing circulating PCSK9,lipoprotein(a)and apolipoprotein C-Ⅲ[J].J Intern Med,2017,281(6):575-585.

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备注/Memo

备注/Memo:
[基金项目]湖南省教育厅科研基金资助重点项目(18A215); 湖南省中医药管理局科研计划项目(D2022016); 湖南中医药大学中医学一流学科开放基金资助项目(2022ZYX09); 湖南中医药大学研究生创新立项课题(2023CX174)
更新日期/Last Update: 2025-02-08