Zhou Feng, Hui Yu, Xu Yongde, Lei Hongen, Yang Bicheng, Guan Ruili, Gao Zhezhu, Xin Zhongcheng, Hou Jianquan
Department of Urology, First Affiliated Hospital of Soochow University, Soochow University, No. 188, Shizi Street, Gusu District, Suzhou, 215006, China.
Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, No. A59, Di'anmen West Street, Xicheng District, Beijing, 100034, China.
Int Urol Nephrol. 2016 May;48(5):657-69. doi: 10.1007/s11255-016-1221-3. Epub 2016 Jan 28.
Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats.
Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured.
We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis.
Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.
勃起功能障碍（ED）是糖尿病（DM）男性患者令人苦恼的并发症。本研究旨在探讨脂肪来源干细胞（ADSCs）联合胰岛素对链脲佐菌素（STZ）诱导的糖尿病大鼠勃起功能障碍的影响。
45只8周龄雄性Sprague-Dawley大鼠腹腔注射STZ（60mg/kg）。诱导8周后，将确诊的糖尿病大鼠随机分为四组：DM+PBS组大鼠一次性海绵体内（IC）注射磷酸盐缓冲盐水（PBS）溶液，DM+ADSCs组大鼠IC注射ADSCs，DM+胰岛素组大鼠每天皮下注射两次中性鱼精蛋白锌胰岛素，DM+ADSCs+胰岛素组大鼠同时接受ADSCs和中性鱼精蛋白锌胰岛素治疗。另外10只正常大鼠作为对照组，接受IC注射PBS。治疗4周后，测量海绵体内压、阴茎组织病理学变化、ADSCs和阴茎的功能蛋白。
我们发现ADSCs表达血管内皮生长因子、TIMP金属肽酶抑制剂1（TIMP-1）和脂多糖诱导的CXC趋化因子（LIX）。与PBS处理的糖尿病大鼠相比，注射ADSCs部分恢复了海绵体内皮和平滑肌含量以及nNOS阳性神经，并减少了阴茎细胞凋亡。胰岛素治疗可进一步调节炎症反应并减少阴茎中晚期糖基化终产物的积累。
ADSCs与胰岛素联合使用比单一治疗更能将糖尿病大鼠的勃起功能障碍和病理变化改善至接近正常水平。
