This study aimed to explore the possibility of miR-423-5p modified adipose-derived stem cell (ADSCs) therapy on streptozotocin (STZ)-induced diabetes mellitus erectile dysfunction (DMED) rats. MiR-423-5p was knocked down in ADSCs. ADSCs, NC-miR-ADSCs and miR-ADSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Normal and high glucose media were supplemented. The supernatant and HUVECs were collected for assessment of eNOS and VEGFa expression, cell proliferation, and apoptosis. HUVECs co-cultured with ADSCs or miR-ADSCs exhibited higher eNOS and VEGFa protein expression levels compared to DM groups. MiR-ADSCs enhanced HUVEC proliferation compared to the ADSCs and NC-miR-ADSCs. Lower apoptotic rates were observed when HUVECs were co-cultured with miR-ADSCs, compared to ADSCs and NC-miR-ADSCs. Fifteen male Sprague-Dawley (SD) rats aged 12 weeks were induced to develop diabetes mellitus by intraperitoneal injection with STZ, and five healthy SD rats were used as normal controls. Eight weeks after developing diabetes, the rats received ADSCs and miR-ADSCs via injection into the corpora cavernosa, whereas normal controls and DM controls were injected with saline. Erectile function and histological assessment of penile tissues were performed 8 weeks after injection. The ICP/MAP indicated that erectile function was impaired in the DM rats compared with the normal group. Injection of ADSCs and miR-ADSCs improved erectile function significantly and was associated with the overexpression of eNOS and VEGFa. MiR-423-5p knockdown in ADSCs ameliorated high glucose-mediated damage to HUVECs and improved erectile function in DM rats by inducing eNOS and VEGFa overexpression, indicating that miR-423-5p may be a potential target in the treatment of DMED.

中文翻译：

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敲低 miR-423-5p 同时升级 ADSCs 中的 eNOS 和 VEGFa 通路并改善糖尿病大鼠的勃起功能

本研究旨在探讨 miR-423-5p 修饰的脂肪干细胞 (ADSCs) 治疗链脲佐菌素 (STZ) 诱导的糖尿病勃起功能障碍 (DMED) 大鼠的可能性。MiR-423-5p 在 ADSC 中被击倒。ADSCs、NC-miR-ADSCs 和 miR-ADSCs 与人脐静脉内皮细胞 (HUVECs) 共培养。补充了正常和高葡萄糖培养基。收集上清液和 HUVEC 用于评估 eNOS 和 VEGFa 表达、细胞增殖和凋亡。与 DM 组相比，与 ADSC 或 miR-ADSC 共培养的 HUVEC 表现出更高的 eNOS 和 VEGFa 蛋白表达水平。与 ADSC 和 NC-miR-ADSC 相比，MiR-ADSC 增强了 HUVEC 增殖。与 ADSCs 和 NC-miR-ADSCs 相比，当 HUVECs 与 miR-ADSCs 共培养时，观察到较低的凋亡率。15只12周龄的雄性Sprague-Dawley（SD）大鼠腹腔注射STZ，5只健康SD大鼠作为正常对照。患糖尿病八周后，大鼠通过注射到海绵体中接受 ADSC 和 miR-ADSC，而正常对照组和 DM 对照组注射盐水。注射后 8 周进行阴茎组织的勃起功能和组织学评估。ICP/MAP表明，与正常组相比，DM大鼠的勃起功能受损。注射 ADSCs 和 miR-ADSCs 显着改善了勃起功能，并且与 eNOS 和 VEGFa 的过表达有关。