摘要
目的:研究精索静脉曲张(VC)及VC高位结扎术(VCT)对大鼠睾丸组织蛋白质组学的影响,并分析差异蛋白和信号通路,观察睾丸组织显微结构变化。方法:选用60只雄性SD大鼠分3组,假手术组,VC组和VCT组,分别于手术操作后4周收集大鼠睾丸组织。质谱分析蛋白质的差异表达,KEGG通路复极化分析蛋白质通路改变,透射电镜观察生精细胞的显微变化。结果:获得有效鉴定及有临床意义的蛋白质共15种,其中RPS24、KIFAP3、HPX、RPL38、TOP2A、PRPF19、TRPM3、RPL32、CNBP、AHSG等蛋白表达上调,RPS9、TKFC、SH3BGRL3、ACAA2、FABP3等蛋白表达下调,而发现的差异通路包括Ⅰ型4-氨基丁酸降解通路、eIF2信号传导通路和Ⅲ型谷氨酸降解通路等,其均与睾丸生长停滞的发病机制相关。电镜下观察,相较于VCT组,VC组大鼠睾丸组织表现为线粒体空泡变性,核仁致密,细胞核膜内陷,不规则等不利于睾丸细胞存活的超微结构改变。结论:VCT可通过改变睾丸细胞内的相关蛋白表达,影响睾丸细胞内基因通路的变化,进而影响睾丸的发育生长。这可能是VC致睾丸损伤、影响睾丸生精功能障碍的原因之一。这些分子途径的改变可以为了解VC提供理论依据,同时也为治疗VC提供了潜在的治疗靶点。
Objective:To study the impacts of varicocele(VC)and varicocelectomy(VCT)on the proteomics of rat testis tissue,and to analyze the differential proteins and signaling pathways,and observe the microstructural changes of the testis tissue.Methods:We selected 60 male SD rats and divided them into a sham operation(SO),a VC model control,and a VCT group.We harvested the testis tissues from the rats at 4 weeks after modeling for determination of the differential protein expressions by mass spectrometry,analysis of the changes in the protein signaling pathways by KEGG pathway repolarization,and observation of the microstructural changes in the spermatogenic cells under the transmission electron microscope(TEM).Results:A total of 15 clinically significant proteins were effectively identified,among which RPS24,KIFAP3,HPX,RPL38,TOP2A,PRPF19,TRPM3,RPL32,CNBP and AHSG were upregulated,while RPS9,TKFC,SH3BGRL3,ACAA2 and FABP3 downregulated.The differential pathways found included the Type-I 4-aminobutyrate degradation pathway,eIF2 signaling pathway,and Type-III glutamate degradation pathway,which were all related to the pathogenesis of testicular growth arrest.Compared with the rats in the VCT group,those of the VC group rats showed ultrastructural changes in the testis tissue under the TEM,such as mitochondrial vacuolar degeneration,dense nucleoli,invagination of cell nuclear membranes,and irregularity,which were detrimental to the survival of testicular cells.Conclusion:VCT affects the development and growth of the testis by altering the expressions of relevant proteins and influencing the changes of the gene pathways in the testicular cells,which may be one of the causes of VC inducing testis injury and testicular spermatogenic dysfunction.The changes in these molecular pathways can provide some theoretical evidence for an insight VC as well as potential therapeutic targets for its treatment.
作者
赵旭嵩
房波
田苍雨
崔岩康
沈天一
王苏春
汤昊
吴猛
徐锋
ZHAO Xu-song;FANG Bo;TIAN Cang-yu;CUI Yan-kang;SHEN Tian-yi;WANG Su-chun;TANG Hao;WU Meng;XU Feng(Department of Urology,Jinling Hospital Affiliated to Nanjing University School of Medicine/General Hospital of Eastern Theater Command,Nanjing,Jiangsu 210002,China;Wujin Hospital of TCM/Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu 213161,China)
出处
《中华男科学杂志》
CAS
CSCD
2024年第12期1098-1104,共7页
National Journal of Andrology
基金
南京大学医学院附属金陵医院面上课题(YYMS2021025)。
