Urantide对ApoE^(-/-)小鼠动脉粥样硬化合并代谢相关脂肪性肝病中α-SMA、OPN的影响  

Effect of Urantide onα-SMA and OPN in ApoE^(-/-)Mice with Atherosclerosis combined with Metabolically Related Fatty Liver Disease

作　　者：黄圣 王途 崔海鹏[1] 邹润 黄慧 赵娟[1] HUANG Sheng;WANG Tu;CUI Hai-peng;ZOU Run;HUANG Hui;ZHAO Juan(Department of Pathophysiology,Chengde Medical University,Chengde,Hebei,067000,China)

机构地区：[1]承德医学院病理生理学教研室,河北承德067000

出　　处：《承德医学院学报》2024年第4期271-276,共6页Journal of Chengde Medical University

基　　金：河北省自然科学基金项目(H2020406011);河北省自然科学基金中医药联合基金重点项目(H2023406017);河北省委组织部青年拔尖人才项目(冀组字【2016】9号);河北省高等学校科学研究青年基金(QN2023017);承德医学院基本科研业务费(KY202123;KY202227);河北省教育厅高校重点学科建设项目(冀教高【2013】4号病理学与病理生理学)。

摘　　要：目的观察Urantide对ApoE^(-/-)小鼠代谢相关脂肪性肝病(MAFLD)中α-SMA、OPN的影响,探讨其在动脉粥样硬化(AS)合并MAFLD中对肝纤维化的治疗作用。方法将ApoE^(-/-)小鼠分为AS模型组、辛伐他汀组、Urantide低、中、高剂量组,C57BL/6为对照组;对照组和AS模型组给予生理盐水20 mg/kg、辛伐他汀组给予辛伐他汀5 mg/kg、Urantide组分别给予Urantide 20 mg/kg、30 mg/kg、40 mg/kg,治疗14d后,HE及油红O染色观察肝脏病理改变;Masson三色染色观察肝脏胶原纤维表达;免疫组化法检测肝脏α-SMA表达及定位;RT-qPCR检测UⅡ/UT系统基因变化;Western blotting检测肝内α-SMA、OPN、UⅡ/UT系统的表达。结果与对照组相比,AS模型组小鼠肝脏出现脂肪变性,油红O染色出现大量脂滴浸润,窦周间隙出现胶原纤维沉积,肝脏α-SMA、OPN、UII、GPR14蛋白表达升高;UII、GPR14 mRNA水平升高;经Urantide治疗后,肝脏脂滴减少、脂肪性病变显著改善,胶原纤维减少,UⅡ/UT系统和α-SMA、OPN表达显著降低。结论Urantide可能通过拮抗UⅡ/UT系统从而改善ApoE^(-/-)小鼠肝脏脂肪变性,达到治疗肝纤维化的作用。Objective To observe the effect of Urantide onα-SMA and OPN in ApoE^(-/-)mice with metabolic-associated fatty liver disease(MAFLD),and to explore its therapeutic effect on liver fibrosis in atherosclerosis(AS)complicated with MAFLD.Methods ApoE^(-/-)mice were divided into AS model group,simvastatin group,low-dose,medium-dose,and highdose Urantide groups.C57BL/6 mice were used as control group.The control group and AS model group were treated with normal saline 20 mg/kg,the simvastatin group was treated with simvastatin 5 mg/kg,and the Urantide group was treated with Urantide 20 mg/kg,30 mg/kg and 40 mg/kg,respectively.After 14 days of treatment,the pathological changes of liver were observed by HE and oil red O staining.Masson trichrome staining was used to observe the expression of collagen fibers in the liver.The expression and localization ofα-SMA in liver were detected by immunohistochemistry.RT-qPCR was used to detect the gene changes of UⅡ/UT system.The expressions ofα-SMA,OPN and UⅡ/UT system in liver were detected by Western blotting.Results Compared with the control group,the mice in the AS model group showed liver steatosis,oil red O staining showed a large number of lipid droplets infiltration,collagen fiber deposition in the periosinusitis space,and the expression ofα-SMA,OPN,UII and GPR14 protein in the liver increased.UII and GPR14 mRNA levels were increased.After Urantide treatment,the lipid droplets and fatty lesions in the liver were significantly reduced,collagen fibers were reduced,and the expressions of UⅡ/UT system,α-SMA and OPN were significantly decreased.Conclusion Urantide may improve hepatic steatosis in ApoE^(-/-)mice by antagonizing the UⅡ/UT system.

关 键 词：代谢相关脂肪性肝病 动脉粥样硬化 肝纤维化 URANTIDE Α-SMA OPN 

分 类 号：R363[医药卫生—病理学]