Castela Angela, Gomes Pedro, Silvestre Ricardo, Guardão Luísa, Leite Liliana, Chilro Rui, Rodrigues Ilda, Vendeira Pedro, Virag Ronald, Costa Carla
Faculty of Medicine, Department of Biochemistry, University of Porto, Porto, Portugal.
Institute for Molecular and Cell Biology of the University of Porto (IBMC-UP), Porto, Portugal.
J Cell Biochem. 2017 Jan;118(1):82-91. doi: 10.1002/jcb.25613. Epub 2016 Jun 13.
Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc.
勃起功能障碍（ED）是糖尿病的一种并发症，糖尿病会导致内皮功能障碍（EDys）并阻碍修复机制。然而，关于内皮祖细胞（EPCs）介导的血管生成与糖尿病相关ED之间联系的信息很少。此外，血糖控制是否对EPCs功能、EPCs调节剂和阴茎血管健康起作用仍有待阐明。我们评估了糖尿病和胰岛素治疗对骨髓（BM）和循环EPCs、睾酮以及全身/阴茎基质衍生因子-1α（SDF-1α）表达的影响。雄性Wistar大鼠分为几组：年龄匹配的对照组、8周链脲佐菌素诱导的1型糖尿病大鼠以及胰岛素治疗的8周糖尿病大鼠。通过流式细胞术检测CD34/CD133/VEGFR2/CXCR4抗原以鉴定EPCs。通过酶联免疫吸附测定法评估全身SDF-1α和睾酮水平。通过免疫组织化学技术评估实验性和人类糖尿病海绵体样本中阴茎SDF-1α蛋白表达。糖尿病动物的骨髓源性EPCs减少，血管壁脱落的假定循环内皮细胞（CECs）增加。胰岛素治疗可挽救这些改变。此外，血糖控制促进全身睾酮和SDF-1α水平升高，糖尿病动物的这些水平显著降低。实验性和人类海绵体糖尿病样本中SDF-1α蛋白表达降低，胰岛素可预防治疗动物的这种作用。胰岛素给药挽救了糖尿病对骨髓功能、CECs水平、睾酮以及血浆/阴茎SDF-1α蛋白表达的影响。这强调了血糖控制在预防糖尿病引起的全身和阴茎EDys中的重要性，通过改善内皮损伤和增加保护途径来实现。《细胞生物化学杂志》118: 82 - 91, 2017。© 2016威利期刊公司
