大鼠良性前列腺增生完全去神经支配后基因表达谱动态变化研究  

Dynamic change in the gene expression profile of rat benign prostate hyperplasia tissue after complete denervation

作　　者：蔡建良 阎乙夫 冯光伟 景硕 CAI Jian-liang;YAN Yi-fu;FENG Guang-wei;JING Shuo(Department of Urology,Beijing Shijitan Hospital,Capital Medical University/Peking University Ninth School of Clinical Medicine,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院泌尿外科/北京大学第九临床医学院

出　　处：《中华男科学杂志》2019年第11期971-977,共7页National Journal of Andrology

基　　金：国家自然科学基金(81070601);北京市自然科学基金(7102106)~~

摘　　要：目的:探索大鼠BPH组织完全去神经支配后进行性萎缩过程中全基因表达谱动态变化情况。方法:29周龄雄性自发性高血压大鼠(SHR,已自发形成BPH)12只,9只手术切断前列腺全部支配神经。分别于手术当天取对照组(C)3只、术后3 d(D3)、7 d(D7)、11 d(D11)SHR各3只,取前列腺腹侧叶进行组织病理学检查和RNA提取,所有RNA样本进行全基因表达谱芯片检测、实时荧光PCR验证和生物信息学分析。结果:完全去神经支配后大鼠BPH组织进行性萎缩。各样本全基因组表达谱芯片检测均成功完成,随机选择的6个差异表达基因的实时荧光PCR结果证实芯片检测可靠。分层聚类分析显示:D3/C表达上调基因108个,下调基因175个;D7/C上调基因462个,下调基因189个;D11/C上调基因548个,下调基因256个。GO功能富集分析显示各比较组差异表达的基因涉及数百上千数量不等的分子功能、生物学进程和细胞组分。Pathway通路富集分析显示各比较组差异表达的基因涉及数百条信号通路,其中多条信号通路在各比较组均能富集到且排名靠前,其涉及的基因大部分都表达上调,且大多数与补体系统激活相关。结论:完全去神经支配后大鼠BPH组织进行性萎缩过程伴随着大量基因的异常表达,这些基因涉及众多的分子功能、生物学进程、细胞组分和信号通路,补体系统的异常激活可能在该进行性萎缩过程中有重要作用。Objective:To investigate the dynamic change in the gene expression profile of the rat BPH tissue with progressive atrophy after complete denervation.Methods:Twelve 29-week-old male rats with spontaneous hypertension and spontaneously developed BPH were used for this study,of which 3 were included in the control(C)group and the other 9 underwent complete denervation of the prostate.At 3,7 and 11 days after operation(the D3,D7 and D11 groups),all the rats were sacrificed and their ventral prostatic lobes harvested for histopathological examination and RNA extraction,and the RNA samples were subjected to whole genome microarray of the expression profile,followed by real-time RT-PCR validation and bioinformatics analysis.Results:Progressive atrophy of the BPH tissue was observed in the rats after complete denervation.Whole genome microarray of the expression profile was successfully performed for all the samples,and its reliability validated by real-time RT-PCR of 6 differentially expressed genes selected randomly.Hierarchical clustering analysis showed 108 up-regulated and 175 down-regulated genes in the differentially expressed ones between the D3 and C groups,462 up-regulated and 189 down-regulated in those between the D7 and C groups,and 548 up-regulated and 256 down-regulated in those between the D11 and C groups.GO functional enrichment analysis indicated that the genes in each differentially expressed gene set participated in hundreds of molecular functions,biological processes and cellular components,while pathway enrichment analysis showed their involvement in hundreds of signaling pathways,of which many were enriched simultaneously in each differentially expressed gene set and ranked as the most enriched ones,and most of the genes involved were up-regulated and related with the activation of the complement system.Conclusion:Large numbers of abnormally expressed genes are involved in the progressive atrophy of rat BPH tissue after complete denervation,and these genes participate in hundreds of molecular func

关 键 词：良性前列腺增生 去神经支配 全基因表达谱 生物信息学分析 大鼠 

分 类 号：R697.32[医药卫生—泌尿科学]