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Identification and characterization of the microrna profile in aging rats with erectile dysfunction

机译:勃起功能障碍衰老大鼠微RNA谱的鉴定与表征

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Introduction: Aging-related erectile dysfunction (A-ED) is a neurovascular and refractory disorder with complicated pathophysiological mechanisms and a high prevalence. MicroRNAs (miRNAs), which modulate a variety of cell functions, may be involved in the pathophysiological processes of this disorder. Aim: To investigate the miRNA profile in the corpus cavernosum (CC) of aging rats with ED, and to analyze the target genes and signaling pathways regulated by the dysregulated miRNAs. Methods: According to the apomorphine test, the experimental animals were divided into three groups: aging rats with ED (group AE), aging rats with normal erectile function (group AN), and young rats as normal controls (group YN). After the erectile functional test, CCs from each group were then collected for histological and molecular measurements. Main Outcome Measures: Intracavernous pressure response to electric stimulation of the cavernous nerve was used to evaluate erectile function. Histological changes within CC were evaluated using immunofluorescent staining. GeneChip array was used to analyze the miRNA expression profiling. The miRNA profilings were further validated by real-time polymerase chain reaction. The TargetScan or DAIAN web platform and DAVID were used for bioinformatic analysis. Results: Accompanied with significantly decreased erectile function, the content of smooth muscle and endothelium within the CC of rats with A-ED was significantly decreased compared with both AN group and YN group. miR-1, miR-200a, miR-203, and miR-206 were found and validated up-regulating with above twofold change in AE group. According to the bioinformatics analysis, the four up-expressing miRNAs could regulate eNOS/NO/PKG and PGE1/PKA pathways through regulating 13 target genes. Conclusions: Four miRNAs were found up-regulated significantly in the CC of rats with A-ED. The four miRNAs might play important roles in the development of A-ED by regulating the eNOS/NO/PKG and PGE1/PKA pathways despite lots of experiments still need to be validated.
机译:简介:衰老相关的勃起功能障碍(A-ED)是一种神经血管和难治性疾病,其病理生理机制复杂且患病率很高。调节多种细胞功能的MicroRNA(miRNA)可能参与了该疾病的病理生理过程。目的:研究衰老大鼠ED的海绵体(CC)中的miRNA谱,并分析miRNA失调调节的靶基因和信号通路。方法:根据阿扑吗啡试验,将实验动物分为三组:ED衰老大鼠(AE组),勃起功能正常的衰老大鼠(AN组)和作为正常对照组的年轻大鼠(YN组)。进行勃起功能测试后,然后收集每组的CC进行组织学和分子测量。主要观察指标:海绵体神经电刺激海绵体压力反应来评估勃起功能。使用免疫荧光染色评估CC内的组织学变化。 GeneChip阵列用于分析miRNA表达谱。通过实时聚合酶链反应进一步验证了miRNA分析。 TargetScan或DAIAN Web平台和DAVID用于生物信息分析。结果:与AN组和YN组相比,A-ED大鼠CC中的平滑肌和内皮细胞含量显着降低,且勃起功能明显降低。在AE组中,发现miR-1,miR-200a,miR-203和miR-206并通过以上两倍的变化证实其上调。根据生物信息学分析,四个表达高的miRNA可以通过调控13个靶基因来调控eNOS / NO / PKG和PGE1 / PKA途径。结论:在A-ED大鼠的CC中发现4种miRNA显着上调。尽管仍需要验证大量实验,但通过调节eNOS / NO / PKG和PGE1 / PKA途径,这四种miRNA可能在A-ED的发展中发挥重要作用。

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