基于IRE1α/XBP1信号通路探讨消木丹对非酒精性脂肪肝病小鼠脂质代谢的影响  

Effects of Xiaomudan Granules on liver lipid metabolism in mice with non-alcoholic fatty liver disease based on IRE1α/XBP1 signaling pathway

作　　者：杨清瑞 李京涛 闫瑞娟 惠建萍 李昕株 雷玉玉 刘海涛 YANG Qingrui;LI Jingtao;YAN Ruijuan;HUI Jianping;LI Xinzhu;LEI Yuyu;LIU Haitao(Xi'an International Medical Center Hospital,Xi'an 710100,China;Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;Qinghai University,Xining 810016,China)

机构地区：[1]西安国际医学中心医院,西安710100 [2]陕西中医药大学附属医院,陕西咸阳712000 [3]青海大学,西宁810016

出　　处：《吉林中医药》2025年第3期337-342,共6页Jilin Journal of Chinese Medicine

基　　金：国家自然科学基金项目(82174330);陕西省科技厅自然科学基金项目(2023-JC-YB-678);陕西省中医药管理局课题(2021-GJ-JG009);陕西中医药大学附属医院科研基金项目(2020MS005)。

摘　　要：目的探讨消木丹颗粒对非酒精性脂肪肝病(HFD)小鼠肝脏脂质代谢的影响及IRE1α/XBP1信号通路的调节机制。方法将60只C57/BL6J雄性小鼠随机分为正常组、模型组、消木丹高、中、低剂量组及二甲双胍组,每组10只。除正常组外,其余各组小鼠采用高脂饮食12周建立非酒精性脂肪肝病小鼠模型,给药组同时按照上述剂量灌胃给药,每日1次,连续8周。采用ELISA法检测肝脏组织TC、TG、FFA、VLDL表达水平;HE染色法观察肝脏组织病理学变化;Western-blot检测肝脏组织中IRE1α/XBP1通路相关蛋白表达;荧光定量PCR法检测GRP78、XBP1、MTP、PDI及ApoB-100 mRNA表达水平。结果消木丹能显著降低非酒精性脂肪肝小鼠TC、TG、FFA、VLDL含量(P<0.05,P<0.01),改善其肝组织结构及脂肪变性,减少肝组织GRP78、XBP1、MTP、PDI及ApoB100蛋白和mRNA的表达以及IRE1ɑ磷酸化(P<0.05或P<0.01)。结论消木丹颗粒可通过抑制IRE1α/XBP1通路及下游蛋白MTP、PDI和ApoB100的表达,缓解肝脏内质网应激,减轻肝脏脂肪沉积。Objective To investigate the effects of Xiaomudan Granules on the liver lipid metabolism in mice of non-alcoholic fatty liver disease(NAFLD)and the regulatory mechanism of the IRE1α/XBP1 signaling pathway in them.Methods An NAFLD mouse model of sixty C57/BL6J male mice was established with a high-fat diet,and then the mice were randomly divided into a model group,Xiaomudan Granules high-,medium-,and low-dose groups and metformin positive group(PC),and the normal control group(NC).The NC group and model group were given normal saline intragastric administrations,while the mice in the three Xiaomudan Granules groups were treated with Xiaomudan Granules at 0.117,0.234,and 0.468 g·kg-1·d-1,respectively,and the PC group were given 0.2 g·kg-1·d-1 metformin,all once a day for eight weeks.The expression levels of TC,TG,FFA,and VLDL in liver tissue were detected by ELISA.The pathological changes in liver tissue were observed by HE staining.Western-blot was used to detect the protein expressions of GRP78,p-IRE1α,XBP1,MTP,PDI,and ApoB100 in liver tissue,whilefluorescent quantitative PCR was used to detect the mRNA expression levels of GRP78,XBP1,MTP,PDI,and ApoB100.Results Xiaomudan Granules significantly decreased the contents of TC,TG,FFA,and VLDL in NAFLD mice(P<0.05 or P<0.01),improved their liver tissue structure and fatty degeneration,reduced the protein and mRNA expression levels of GRP78,XBP1,MTP,PDI,and ApoB100,and reduced IRE1αphosphorylation in liver tissue(P<0.05 or P<0.01).Conclusion Xiaomudan Granules can alleviate liver endoplasmic reticulum stress and reduce liver fat deposition by inhibiting the expression of the IRE1α/XBP1 pathway and downstream proteins MTP,PDI,and ApoB100.

关 键 词：非酒精性脂肪肝 消木丹颗粒 IRE1α/XBP1信号通路 

分 类 号：R575.5[医药卫生—消化系统]