FXR/FMO3/TMAO脂代谢通路在复合应激勃起功能障碍大鼠模型中的调控作用及伊木萨克片干预的机制研究  

Regulatory effect of the lipid metabolic pathways of TMAO,FM03 and FXR on compound stress-induced ED in rats and mechanisms of Yimusake intervention

作　　者：刘凤霞 袁千茹 田艳南 艾孜孜·热合曼 斯依提·阿木提 刘文娟 阿地力江·伊明 LIU Feng-xia;YUAN Qian-ru;TIAN Yan-nan;AIZIZI Reheman;SIYITI Amuti;LIU Wen-juan;ADLIJIANG Yiming(Department of Human Anatomy,School of Basic Medical Sciences,Urumqi,Xinjiang S300 W,China;The First School of Clinical Medicine,Xinjiang Medical University,Urumqi,Xinjiang S300 W,China)

机构地区：[1]新疆医科大学基础医学院人体解剖学教研室,新疆乌鲁木齐830011 [2]新疆医科大学第一临床学院,新疆乌鲁木齐830011

出　　处：《中华男科学杂志》2020年第2期106-110,共5页National Journal of Andrology

基　　金：新疆医科大学第13期大学生创新训练计划(CX2018074);新疆自治区“十三五”重点学科(2050205)。

摘　　要：目的:研究FXR/FMO3/TMAO脂代谢通路在复合应激ED大鼠模型中的调控作用及伊木萨克片干预的机制. 方法:在代谢组学筛查结果的基础上,采用核磁共振波谱仪检测正常对照组(n=30)、复合应激ED组(ED组,n=30)和伊木萨克片干预组(n=30)大鼠血清中的TMAO浓度;Western印迹检测FXR1/2、FMO3在各组大鼠肝脏组织中表达水平的变化. 结果:①ED组大鼠血清中TMAO浓度[(46.64±5.16) μg/ml]较正常对照组[(34.98±3.69) μg/ml]显著升高(P<0.01),伊木萨克片干预组[(39.63±4.81) μg/ml]较ED组显著下降(P<0.01).②Western印迹结果发现,ED组大鼠肝脏中FMO3蛋白相对表达量(1.75±0.90)较正常对照组(0.86±0.62)显著升高(P<0.01),伊木萨克片干预组(1.05±0.38)较ED组显著降低(P<0.05).③Western印迹结果发现,ED组大鼠肝脏组织中FXR1蛋白相对表达量(1.29±0.38)较正常对照组(0.78±0.25)显著升高(P<0.01),伊木萨克片干预组(1.07 ±0.42)较ED组显著降低(P<0.05);ED组FXR2蛋白相对表达量(1.90±0.63)较正常对照组(0.42±0.27)显著升高(P<0.01),伊木萨克片干预组(1.04±0.46)较ED组显著降低(P<0.01).结论:FXP/FMO3/TMAO脂代谢通路在复合应激ED大鼠模型中发生显著增高,而伊木萨克片干预后可以改善此变化,提示此药可能通过调控FXR/FMO3/TMAO脂代谢通路对大鼠阴茎勃起功能起到保护作用.Objective:To study of the regulatory effects of the lipid metabolic pathways of trimethylamine-N-oxide(TMAO),flavin-containingmonooxidase 3(FM03)and farnesoid X receptor(FXR)on compound stress-induced ED(CSED)rats and the mechanisms of Yimusake Tablets(YMSK)intervention.Methods:Based on the results of metabonomics analysis,we determined the concentration of TMAO in the serum of the rats in the normal control(n=30),the CSED model control(n=30)and the YMSK intervention group(intragastrical administration of YMSK at 250 mg/kg once daily for 2-3 weeks after modeling,n=30)by nuclear magnetic resonance(NMR)spectroscopy test.We also detected the expressions of the FM 03,FXR1 and FXR2 proteins in the liver tissue of the three groups of rats by Western blot.Results:The serum TMAO level was significantly elevated in the CSED model control compared with that in the normal control group([46.64±5.16]vs[34.98±3.69]μg/mL,P<0.01)but remarkably decreased after YMSK intervention([39.63土4.81]μg/mL)in comparison with that in the CSED model control group(P<0.01).The rats in the CSED model control group,compared with the normal controls,showed significantly upregulated expressions of FM03(1.75±0.90vs0.86±0.62,P<0.01),FXR1(1.29±0.38vs0.78±0.25,P<0.01)and FXR2 in the liver tissue(1.90±0.63vs0.42±0.27,P<0.01),but all the three expressions were markedly decreased after YMSK intervention(FM03:1.05±0.38,P<0.05;FXR1:1.07±0.42,P<0.05;FXR2:1.04±0.46,P<0.01)as compared with those in the CSED model control group.Conclusion:The lipid metabolic pathways of TMAO,FM03 and FXR underwent significant changes in the rat model of compound stress-induced ED,which could be improved by YMSK intervention,suggesting that YMSK may play an important role in protecting erectile function by regulating the lipid metabolic pathways of TMAO,FM03 and FXR.

关 键 词：勃起功能障碍 氧化三甲基胺 含黄素单氧化酶3 法尼酯X受体 大鼠 

分 类 号：R698.1[医药卫生—泌尿科学]