Implications for differentiation of endogenous stem cells: therapeutic effect from icariside II on a rat model of postprostatectomy erectile dysfunction.
Implications for differentiation of endogenous stem cells: therapeutic effect from icariside II on a rat model of postprostatectomy erectile dysfunction.
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DOI：
10.1089/scd.2014.0380
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发表时间：
2015-03
影响因子：
4
通讯作者：
Yongde Xu;R. Guan;H. Lei;Zhe-zhu Gao;Hui-xi Li;Y. Hui;Feng Zhou;Lin Wang;Guiting Lin;Z. Xin
中科院分区：
文献类型：
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作者：
Yongde Xu;R. Guan;H. Lei;Zhe-zhu Gao;Hui-xi Li;Y. Hui;Feng Zhou;Lin Wang;Guiting Lin;Z. Xin
内源性干细胞(SCs)的自我更新和分化对于成体组织的动态平衡和内在修复能力是必不可少的。在这项研究中，我们假设阴茎含有少量的内源性干细胞，这可能有助于修复受损的勃起功能。本研究用新生雄性大鼠60只，用5-乙炔-2-脱氧尿苷(EDU；50 mg/kg)腹腔注射示踪内源性SCs。12周后，48只大鼠双侧海绵体神经损伤，随机分为溶剂组(溶剂组)和淫羊藿苷II组(分别为0.5、1.5和4.5 mg/kg/d)。12只假手术大鼠接受赋形剂治疗，并作为对照组。结果表明，与赋形剂组相比，ICA II治疗组明显恢复了勃起功能，有效地防止了正常神经解剖结构的扭曲、平滑肌萎缩和胶原沉积。3个ICA II治疗组共表达EDU和分化表型(α-SMA或雪旺细胞标记S100)的标记保留细胞(LRC)数量明显高于赋形剂组，且呈剂量依赖关系。此外，阴茎组织中p38丝裂原活化蛋白激酶(MAPK)活性的变化趋势与分化后的LRCs数量变化趋势一致。综上所述，这些结果提示ICA II改善勃起功能和病理改变的潜在机制可能与促进内源性SCs分化有关，这种分化可能受p38 MAPK信号通路的调控。
Self-renewal and differentiation of endogenous stem cells (SCs) are essential for adult tissue homoeostasis and intrinsic healing capacity. In this study, we hypothesize that penis contains a small population of endogenous SCs, which might help rejuvenation of damaged erectile function. In this study, 60 newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous SCs. Twelve weeks later, 48 rats underwent bilateral cavernous nerves injury and were randomized into gavage feeding of solvent (vehicle group) or icariside II (0.5, 1.5, and 4.5 mg/kg/day, respectively). Twelve sham-operated rats received vehicle treatment and served as control. The treatments were continued for 4 weeks followed by a washout period of 72 h. Results showed that ICA II treatment significantly restored erectile function and effectively prevented distortion of normal neural anatomy, smooth muscle atrophy, and collagen deposition compared with the vehicle group. The numbers of label-retaining cells (LRCs) coexpressing EdU and differentiated phenotypes (smooth muscle marker α-SMA or Schwann cell marker S100) were significantly higher in the three ICA II-treated groups than those in vehicle group in a dose-dependent manner. In addition, the changing trend of p38 mitogen-activated protein kinase (MAPK) activity in the penis between groups was same as that of the number of differentiated LRCs. Together, these results suggest that the underlying mechanisms of ICA II in ameliorating erectile function and pathological changes appear to involve enhanced endogenous SCs differentiation, which might be regulated by p38 MAPK signaling pathway.