Hu Chao, Dong Yin-Ying, Dong Ye-Hao, Cui Jie-Feng, Dai Ji-Can
Department of Urology, Affiliated Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, P.R. China.
Department of Oncology, Institute of Liver Cancer, Affiliated Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Mol Med Rep. 2015 Apr;11(4):2781-8. doi: 10.3892/mmr.2014.3112. Epub 2014 Dec 18.
The aim of the present study was to explore the regulation status of genes in oxidative stress (OS)‑induced endothelial dysfunction and to elucidate the mechanism of action of OS‑associated genes, which induce cavernosal endothelial dysfunction in erectile dysfunction (ED). OS was established in purified cavernosal endothelial cells (CECs) using xanthine/xanthine oxidase and the differentially expressed OS‑associated genes were analyzed using gene microarrays. In addition, an ED rat model was established through bilateral internal iliac artery ligation with hyperlipidemia and was verified by an intracavernosal pressure test. The selected OS‑associated genes were validated in the CECs and ED rat model using reverse transcription‑quantitative polymerase chain reaction. Student's t‑test and one‑way analysis of variance were performed using SBC analysis system. Gene microarray analysis revealed that 13090 (31.92%) genes were expressed in the control group, whereas 12039 (29.35%) genes were expressed in the treated group. The cut‑off value for differential expression was set at 2.0 fold‑change and 2480 genes were found to be differentially expressed compared with the control group. Of these cells, 1454 were upregulated and 1026 were downregulated. Cluster analysis identified relevant cell signaling pathways that were hypothesized to be significant in OS‑associated endothelial dysfunction, including the cytokine‑cytokine receptor interactions, nitrogen metabolism, coagulation cascades and cell adherens. Cxcl12, Tgfbr1, Asns, Bdkrb1 and Cdh3 genes showed a corresponding variation in the CECs and ED rat model compared with the results of the gene microarray analysis. In conclusion, in the present study, the network of differentially expressed genes and OS‑associated signaling pathways identified using gene microarray analysis were validated in the CECs and ED rat model. The results indicated that OS may lead to endothelial dysfunction through certain cell signaling pathways, inducing ED. However, further functional verification is required in order to elucidate the underlying mechanisms of OS‑associated cell signaling pathways in ED.
本研究的目的是探讨氧化应激（OS）诱导的内皮功能障碍中基因的调控状态，并阐明与OS相关的基因诱导勃起功能障碍（ED）中海绵体内皮功能障碍的作用机制。使用黄嘌呤/黄嘌呤氧化酶在纯化的海绵体内皮细胞（CEC）中建立OS，并使用基因微阵列分析差异表达的与OS相关的基因。此外，通过双侧髂内动脉结扎合并高脂血症建立ED大鼠模型，并通过海绵体内压试验进行验证。使用逆转录-定量聚合酶链反应在CEC和ED大鼠模型中验证所选的与OS相关的基因。使用SBC分析系统进行学生t检验和单因素方差分析。基因微阵列分析显示，对照组中有13090个（31.92%）基因表达，而处理组中有12039个（29.35%）基因表达。差异表达的截断值设定为2.0倍变化，发现与对照组相比有2480个基因差异表达。在这些细胞中，1454个上调，1026个下调。聚类分析确定了相关的细胞信号通路，这些通路被认为在与OS相关的内皮功能障碍中具有重要意义，包括细胞因子-细胞因子受体相互作用、氮代谢、凝血级联反应和细胞黏附。与基因微阵列分析结果相比，Cxcl12、Tgfbr1、Asns、Bdkrb1和Cdh3基因在CEC和ED大鼠模型中表现出相应的变化。总之，在本研究中，使用基因微阵列分析确定的差异表达基因网络和与OS相关的信号通路在CEC和ED大鼠模型中得到了验证。结果表明，OS可能通过某些细胞信号通路导致内皮功能障碍，从而诱发ED。然而，为了阐明与OS相关的细胞信号通路在ED中的潜在机制，还需要进一步的功能验证。
