Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats
Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats
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DOI：
10.1007/s11255-016-1221-3
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发表时间：
2016-01
影响因子：
2
通讯作者：
F. Zhou;Y. Hui;Yongde Xu;H. Lei;Bicheng Yang;R. Guan;Zhe-zhu Gao;Z. Xin;Jianquan Hou
中科院分区：
文献类型：
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作者：
F. Zhou;Y. Hui;Yongde Xu;H. Lei;Bicheng Yang;R. Guan;Zhe-zhu Gao;Z. Xin;Jianquan Hou
勃起功能障碍(ED)是男性糖尿病(DM)患者的一种令人痛苦的并发症。目的探讨脂肪干细胞(ADSCs)联合胰岛素对链脲佐菌素(STZ)诱导的糖尿病大鼠ED的影响。方法8周龄雄性SD大鼠45只，给予STZ(60 mg/kg)腹腔注射。诱导8周后，将糖尿病大鼠随机分为4组：DM+PBS组一次性海绵体内注射磷酸盐缓冲盐水(PBS)，DM+ADSCs组IC注射ADSCs，DM+ADSCs组皮下注射中性鱼精蛋白Hagedorn，DM+ADSCs+Insulin组同时接受ADSCs和中性鱼精蛋白Hagedorn治疗。另取10只正常大鼠作为对照组，接受PBS注射。结果培养的ADSCs表达血管内皮生长因子、TIMP金属多肽抑制物1(TIMP-1)和脂多糖诱导的CXC趋化因子(Lix)。与PBS治疗的糖尿病大鼠相比，ADSC注射部分恢复了阴茎海绵体内皮细胞和血管内皮细胞的含量和nNOS阳性神经，减少了细胞凋亡。胰岛素治疗可进一步调节炎症反应，减少晚期糖基化终产物在阴茎中的蓄积。结论ADSCs联合胰岛素治疗可使糖尿病大鼠勃起功能障碍和病理改变恢复到接近正常水平。
PurposeErectile 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.MethodsForty-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.ResultsWe 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.ConclusionsBetter than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.