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去交感神经支配后大鼠良性增生前列腺组织基因表达谱动态变化

The dynamic change of gene expression profiles of rats' benign prostate hyperplasia tissues after denervation of sympathetic nerve

摘要目的 探讨去交感神经支配后大鼠良性前列腺增生(BPH)组织全基因表达谱动态变化.方法 29周龄雄性自发性高血压大鼠(已自发形成BPH)12只,9只手术切断前列腺交感腹下神经来源支.正常对照组(N)、术后3d(D3)、11d(D11)、21d(D21) SHR大鼠各3只,取前列腺腹侧叶进行组织病理学检查和RNA提取,RNA样本进行全基因表达谱芯片检测、实时定量聚合酶链反应(Real-time PCR)验证和生物信息学分析.结果 去交感神经支配后大鼠BPH组织中平滑肌出现一过性结构和功能受损.基因表达谱芯片检测完成顺利,Real-time PCR证实芯片结果可靠.分层聚类分析显示:D3/N基因表达上调318个,下调117个;D11/N上调192个,下调66个;D21/N上调44个,下调92个.GO功能和Pathway通路富集分析显示差异表达基因涉及的分子功能、生物学进程、细胞组分和信号通路随术后时间的延长而减少,早期主要与细胞对损伤、应激的反应、炎症、免疫等相关,后期主要与组织成分、细胞功能的修复相关.术后早期富集靠前的信号通路多与补体系统的激活相关,且涉及的基因均表达上调.结论 去交感神经支配对大鼠BPH组织(平滑肌为主)分子水平的影响为一过性,该系列分子事件中补体系统的异常激活可能有重要作用.

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abstractsObjective To investigate the dynamic change of gene express.ion profiles of rats' benign prostate hyperplasia (BPH) tissues after denervation of sympathetic nerve.Methods Twelve spontaneous hypertension rats (SHR),male,29 weeks old,3 for normal control (N),9 were cut the adrenergic inferior epigastric innervation to prostate.Three N,3 SHR 3 days after operation (D3),3 D11 and 3 D21 were sacrificed and collected the ventral lobe of prostate for histopathological examination,RNA extraction,gene expression profiles microarray,real-time quantitative polymerase chain reaction (Real-time PCR)and bioinformatics analysis.Results The smooth muscle in rats' BPH tissues presented a transient structure and function damage after losing the sympathetic innervations.Gene expression profiles microarray tests were finished successfully,their reliability were verified by the real-time PCR.Clustering analysis indicated that the number of up-regulated gene and down-regulated gene in gene set D3/N were 318,117,D11/N were 192,66 and D21/N were 44,92,respectively.GO function and Pathway enrichment analysis indicated that these differentially expressed genes were involved in numerous molecular function,biological progress,cellular compartment and signal pathway,the numbers also decreased with the extension of time.The GO function and signal pathway were related with inflammation,immune response and cellular response to injure and stress at early stages,related with repairmen of tissue compartment and cellular function in late period.Most of the top ranked signal pathways at early stages had relationship with the activation of complement system,and genes involved were up-regulated.Conclusion The impact of denervation of sympathetic nerve for rats' BPH tissue (mainly smooth muscle) in molecular level also is transient,and the abnormal activation of complement system seems to play a important role in the serial molecular events.

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栏目名称 实验研究
DOI 10.3760/cma.j.issn.1001-9030.2019.05.036
发布时间 2019-06-19
基金项目
国家自然科学基金 北京市自然科学基金(7102106)National Natural Science Foundation of China Beijing Municipal Natural Science Foundation
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