复合应激性ED大鼠及伊木萨克片干预后阴茎组织差异表达蛋白的生物信息学分析  

Differentially expressed proteins in the penile tissue of rats with compound stress-induced ED after intervention with Yimusake Tablets: A bioinformatics analysis

作　　者：马文静 张盼盼 斯依提·阿木提 毛吾兰·买买提依明 阿地力江·伊明 西尔艾力·买买提新疆医科大学基础医学院病理生理学教研室 刘文娟 MA Wen-jing;ZHANG Pan-pan;SIYITAmuti;MAOWULAN Maimaitiyiming;ADIIJJIANG Yiniing;XIERAILI Maimaiti;LIU Wen-juan(Central Laboratory,School of Basic Medicine,Xinjiang Medical University,Urumqi,Xinjiang 830011,China;Department of Human Anatomy,School of Basic Medicine,School of Basic Medicine,Xinjiang Medical University,Urumqi,Xinjiang 830011,China;Department of Biology,School of Basic Medicine,Xinjiang Medical University,Urumqi,Xinjiang 830011,China;Departmen of Pathologic Physiology,School of Basic Medicine,Xinjiang Medical University,Urumqi,Xinjiang 830011,China)

机构地区：[1]新疆医科大学中心实验室 [2]新疆医科大学基础医学院人体解剖教研室 [3]新疆医科大学基础医学院病理生理学教研室

出　　处：《中华男科学杂志》2019年第12期1066-1076,共11页National Journal of Andrology

基　　金：新疆维吾尔自治区“十三五”重点学科(高原学科)项目(2050205);新疆维吾尔自治区自然科学基金项目(2017D01C239)~~

摘　　要：目的:利用iTRAQ联合LC-MS-MS技术和IPA生物信息平台寻找复合冷应激ED大鼠阴茎组织中特异性蛋白标志物以及药物干预靶点蛋白,并探讨该病的发生发展的分子机制。方法:取80只性功能正常的雄性大鼠造模,建立复合应激大鼠模型,筛选ED大鼠后,分为正常组(N)(n=10)、ED组(n=15)和伊木萨克片干预组(伊木萨克组)(n=15)共3组,取阴茎组织,提取蛋白质,进行iTRAQ标记结合LC-MS-MS蛋白质组学筛查与鉴定,应用IPA分析平台对大鼠阴茎组织差异蛋白进行生物信息学分析。结果:ED组中获得48种差异表达蛋白,伊木萨克组获得29种差异表达蛋白。IPA分析ED组差异表达蛋白质中与血管内皮功能相关蛋白质18种;与平滑肌活动相关蛋白质5种;与炎症相关蛋白质4种;参与的生物学过程主要集中在糖代谢和酒精分解代谢等;涉及的通路主要是糖代谢通路、钙信号通路和RXR激活通路等。伊木萨克组差异表达蛋白质中与血管内皮功能相关蛋白质5种;与平滑肌活动相关蛋白质1种;与炎症相关蛋白质4种;参与的生物学过程主要为糖代谢、血管扩张和急性期反应等;涉及的信号通路为糖代谢通路、RXR激活通路和急性期反应信号通路等。ED组和伊木萨克组差异蛋白中共获得与ED疾病相关的标志物7种:胶原α-1(III)链(COL3α1)、胶原α-1(I)链(COL1α1)、胶原α-2(I)链(COL1α2)、T-激肽原-1(MAP1)、甘油醛-3磷酸脱氢酶(GAPDH)、双链蛋白聚糖(BGN)以及肌球蛋白-11(MYH11)。结论:阴茎组织中血管内皮及平滑肌功能改变可能是复合应激性ED发生发展的关键机制,并与炎症相关;获得的差异蛋白通过相互作用以及参与相关的信号通路影响阴茎的正常勃起,上述7种蛋白可作为复合应激ED大鼠阴茎组织标志物,MAP1、GAPDH、BGN和MYH11蛋白可能可以作为伊木萨克片药物干预的靶点蛋白。Objective:To search for specific protein makers and target proteins for intervention with Yimusake Tablets(YT)in the penile tissue of rats with ED induced by compound cold stress and explore the molecular mechanisms underlying the development and progression of ED.Methods:Eighty adult male rats were screened and divided into three groups,normal control(n=10),ED model control(n=15)and YT intervention(n=15).The model of compound cold stress-induced ED was established in the latter two groups,and meanwhile the animals in the YT intervention group were treated with oral YT for 2 weeks.After that,proteins were extracted from the penile tissues of the rats for screening and identification by iTRAQ labeling combined with LC-MS-MS proteomics,and the IPA bioinformatics software was used for analysis of differentially expressed proteins.Results:A total of 48 differentially expressed proteins were identified from the penile tissue of the ED model controls,of which 18 were associated with endothelial function,5 with smooth muscle activity and 4 with inflammation,involving the biological processes of glucose metabolism and alcohol catabolism and the signaling pathways of glucose metabolism,calcium and RXR activation.In comparison,29 differentially expressed proteins were identified from the rats in the YT intervention group,of which 5 were associated with endothelial function,1 with smooth muscle activity and 4 with inflammation,involving the biological processes of glucose metabolism,vasodilation and acute-phase response and the signaling pathways glucose metabolism,RXR activation and acute-phase response.Seven ED-associated candidate biomarkers were obtained from the differentially expressed proteins in the ED model control and YT intervention group,including Collagen alpha-1(III)chain(COL3α1),Collagen alpha-1(I)chain(COL1α1),Collagen alpha-2(I)chain(COL1α2),Glyceraldehyde-3-phosphate dehydrogenase(GAPDH),T-kininogen 1(MAP1),Biglycan(BGN),and Myosin-11(MYH11).Conclusion:Changes of vascular endothelial and smooth muscle f

关 键 词：环境激素 冷应激 勃起功能障碍 IPA生物信息学分析 组织标志物 伊木萨克片 

分 类 号：R339.21[医药卫生—人体生理学]