S100A6基因修饰的骨髓间充质干细胞移植治疗糖尿病性勃起功能障碍的机制研究

Reduced function of the corpus cavernosum endothelial cells (CCECs) is closely associated with the progression of diabetic erectile dysfunction (DED). To study what mechanism is responsible for the injury of CCECs and how to protect and reverse the function of CCECs from the injury have become to the hot research field now. Our previously proteoimcs study has found that S100A6, a novel factor may play an important role in CCECs injury, was significantly decreased in the corpus cavernosum tisse of DED rat. Overexpression of S100A6 in vitro and in vivo can significantly improve the viability and activity of CCECs, and erectile ability of rat, but the mechanism underlying these processes remains obscure. In this study, we plan to elucidate the potential regulatory role of S100A6 in CCECs. Furthermore, this study is designed to investigate the effect of S100A6 adenovirus-transfected bone marrow mesenchymal stem cells (BM-MSCs) on improving erectile function in diabetic rats, and to assess the feasibility of combinating stem cells and gene transfection as a new stratagy in treating of DED. We suggested that this project is value to us improving our understanding of DED.

糖尿病性勃起功能障碍（DED）的发生和发展与阴茎海绵体内皮细胞（CCECs）功能损害有着密切关系。因此研究CCECs的损伤机制、针对CCECs功能的损伤进行保护和修复，是当前的研究热点。我们前期采用蛋白质组学方法从源头筛选出了与CCECs受损密切相关的因子（S100A6）。发现S100A6在DED大鼠海绵体组织中表达明显下调；过表达S100A6能显著改善CCECs的生长状态及功能，以及DED大鼠的勃起功能。但是有关S100A6在CCECs内的作用机制尚不清楚。因此，本研究将在体外实验和动物模型中进一步阐述S100A6在CCECs中的作用及其详细调控机制；并利用S100A6基因修饰具有组织修复功能的骨髓间充质干细胞，探索和验证其作为DED干细胞治疗新手段的可行性与疗效，为DED治疗提供新的措施和思路。本研究对于阐明DED的发病机制及提高其治疗水平具有重要的理论价值和现实意义。

勃起功能障碍（ED）严重影响患者的身心健康和生活质量。目前，ED的发病机制仍不清楚，治疗效果不佳。ED的发生和发展与阴茎海绵体内皮细胞（CCECs）、平滑肌细胞（CCSMCs）和神经的功能损害都有着密切的关系。前期我们使用蛋白质组学的研究方法发现了可能与CCECs损伤密切相关的因子S100A6，并计划通过基因修饰干细胞的方式探索其对DED的治疗作用。本研究，我们通过体外对CCECs氧化应激，以及神经损伤的模型，进一步使用蛋白质组的方法筛选验证了HMOX1等新的与CCECs损伤相关的分子；构建了S100A6和hNGFβ基因修饰的干细胞，进一步验证出hNGF-β基因修饰的干细胞抑制大鼠阴茎海绵体组织的细胞纤维化和细胞凋亡，改善海绵体的组织结构，显著改善大鼠的勃起功能障碍。本研究，为基于基因修饰干细胞治疗ED奠定了实验研究的基础。本项目研究，共发表论文4篇，综述2篇，其中SCI论文3篇，另有待发表论文2篇，完成了预期的目标。