Mn-SOD修饰脂质干细胞通过隧道纳米管转运线粒体对糖尿病性ED氧化应激损伤的修复机制

课题组前期研究发现，糖尿病性勃起功能障碍（DED）大鼠阴茎海绵体局部存在明显线粒体氧化应激损伤，抗氧化剂和脂质干细胞（ADSCs）均可以部分改善DED病理损害和勃起功能，但是两种治疗都存在一定局限。最近研究发现，细胞之间存在隧道纳米管（TNT），内皮祖细胞将线粒体等细胞器和其他物质通过TNT转运到处于应激状态的细胞内，提高应激细胞的防御抵抗力。锰超氧化物岐化酶（Mn-SOD）是存在于线粒体中的抗氧化酶。我们拟使用Mn-SOD基因修饰的ADSCs治疗DED，观察Mn-SOD/ADSCs是否可以通过TNT转运线粒体和高表达的Mn-SOD到阴茎海绵体局部内皮细胞和平滑肌细胞内，帮助靶细胞对抗氧化应激损伤，重新建立自由基代谢平衡，从而获得更好的治疗DED效果。干细胞通过TNT，"直接注射""细胞保护剂"到阴茎海绵体局部靶细胞内，治疗DED的作用机制有十分重要的研究价值。

The mechanisms involved in diabetes associated erectiel dysfunction (ED) are complicated. Our previous studies found that oxidative stress in the corpus cavernosum of diabetic rats played a important role in the development of diabetic ED and anti-oxidative therapy partly repaired the pathological injury.It has been demonstrated that intracavernous injection of adipose tissue-derived stem cells (ADSCs) partly improved erectile function in several ED animal models. However, both the anti-oxidative stress therapy and ADSCs injection have some limitations. Recently, tunneling nanotubule (TNT) has been found between cells. Endothelial progenitor cells (EPCs) transport mitochondria to the other cells in oxidative stress status to protect them. We hypothesize that intracavernous injection of ADSCs not only replace the injured cells, but also transport mitochondria to the endothelial cells and smooth muscle cells which are in oxidative stress status within the corpus cavernosum of diabetic rats. With this anti-oxiative effects, ADSCs could cure the injured cells in corpus cavernosum and improve erectile function of diabetic rats. Manganese-superoxide dismutase (Mn-SOD)is a kind of anti-oxidative enzyme wihtin the mitochondria. Mn-SOD gene modified ADSCs could express high level of Mn-SOD and improve the anti-oxidative effects. The proposed project may open a new window for ADSCs improving erectile function.