中文摘要
勃起功能障碍(ED)是心血管疾病的重要早期预警症状,其中糖尿病ED(DED)占器质性ED的30%以上,如何防治DED日益得到重视。临床上常用一线、二线等治疗均不能从根本上修复DED的病理变化。脂肪干细胞(ADSC)来源丰富且取材简单,自体移植没有伦理学问题,为DED的治疗带来了新的契机。为此,我们提出假说:ADSC 3D微组织可以从根本上改善DED的病理变化,从而治疗DED。为验证该假说,我们拟应用DED大鼠模型,研究DED神经病变的发生发展的变化,应用经EdU标记的ADSC 3D微组织注射DED大鼠阴茎海绵体,并监测海绵体内压等勃起功能变化。揭示ADSC 3D微组织改善DED神经病变发生发展的作用,为干细胞治疗DED提供新的理论依据和技术支持,为DED的防治及新药开发提供新的思路。
英文摘要
The incidence of erectile dysfunction (ED) is increasing and it is one of the earlist warning symptoms of cardiovascular diseases. ED does great harm to health and familie harmonie of the patients. The diabetic ED (DED) reached more than 30% of the organic ED. However, the recent therapeutic approaches are usually demand based prior to sexual activity that could not reverse the pathophysiological conditions. Adipose-derived stem cells (ADSC) can be easily isolated and have lots of sources, and autologous transplantation has no ethic problems, which has become an important source of seed cells in clinical practice. We propose the hupothesis: ADSC 3D-MTs can fundamentally improve the pathological changes of DED, and thus treat DED. In the earlier study, applicants solved the problem of retention of stem cells, using ADSC to spontaneously form a three dimensional micro tissues (3D-MTs) structure. The aim of this study is to establish an ideal DED rat model, and study the changes of DED neuropathy. We will study the changes of 3D-MTs (labelled with EdU) in the rat penile corpus cavernosum to prove its therapeutic efficacy and advantages in treating DED rat model. This project will provide a new theoretical basis and technical support for stem cell treatment for DED. All these research will lay the basis of drug development in the treatment of DED.
结题摘要
勃起功能障碍(ED)是心血管疾病的重要早期预警症状,其中糖尿病ED(DED)占器质性ED的30%以上,如何防治DED越来越得到重视。临床上常用一、二线等治疗均不能从根本上修复逆转DED的病理学变化。脂肪干细胞(ADSC)来源丰富取材简单,自体移植没有伦理学问题,为DED的治疗带来新了的契机。为此,我们提出假说:ADSC 3D微组织可以从根本上改善DED的病理变化,从而治疗DED。 本研究中我们利用DED大鼠模型,采用组织学、生物信息学、realtimePCR、Westernblot等手段,从分子、细胞、组织以及动物水平等多层次进行研究,构建了合理的规范的糖尿病勃起功能障碍动物模型,探明糖尿病勃起功能障碍阴茎海绵体组织病理学变化规律,尤其是糖尿病性阴茎内皮、肌肉以及神经损伤的时间相关性过程,发现DED大鼠盆底神经在BDNF培养下神经纤维生长速度显著低于正常组;DED大鼠盆底神经组织出现粗面内质网肿胀及线粒体空泡化,溶酶体数目显著增多;阴茎海绵体神经束出现轴索肿胀及轴突空泡化等病理变化。 同时比较了大鼠ADSC与基于ADSC的ADSC 3D微组织的特性及蛋白水平的差异,同时通过阴茎海绵体内注射的方法,将ADSC及ADSC 3D微组织用于治疗DED大鼠,分析比较相关功能学和组织病理学改变,ADSC 3D微组织组海绵体平滑肌(α-SMA)及内皮(vWF、VEGF)、nNOS表达显著提高。初步探明ADSC 3D微组织在受损阴茎组织结构和功能中的修复作用,评估其在治疗中的安全性和有效性;为干细胞治疗DED提供新的理论依据和技术支持,为DED的防治及新药开发提供新的思路。
