Comp-Angiopoietin-1 与脂肪干细胞联用长效改善勃起功能障碍的实验研究

Erectile dysfunction affects up to 52% in 40-70 old men which is closely related with vascular risk factors and vascular disease. But recently developed oral medication (PDE5 inhibitors) is smooth muscle relaxant which induces temporary erection and cannot fundamentally improve penile vascular pathological changes. 30%-50% of patients with ED respond poorly to it. Presently many researchers attempted to develop a fundamental therapy of ED with a single angiogenesis factor, but it has not been in the clinical trials. This suggests that single angiogenic factor cannot fundamentally cure penile vascular disease. Our previous study has shown that adipose tissue-derived stem cells can promote angiogenesis better than bone marrow stem cells. We used them to induce penile neoangiogenesis in diabetic ED mouse model. In ED mouse model induced by hypercholesterolemia, intracavernous injection of adenovirus Comp-Angiopoietin-1 and Comp-Angiopoietin-1 protein can recovery the erectile function up to 8 weeks after injection. The objective of this study is to develop an effective neoangiogenesis technique using multiple approach methods(cell/gene/protein theraphy) and fundamentally cure ED.

勃起功能障碍（erectile dysfunction, ED）在中、老年男性中的发病率达到52%，ED与血管高危因子及血管疾病密切相关。但目前主要开发及应用的口服药物（PDE5抑制剂）只是诱发一时性勃起的平滑肌舒张剂，不能改善阴茎血管病变，并在30-50% ED患者中治疗效果不佳。最近很多研究者试图利用单一血管生成因子开发ED的长期治疗法，但还没有一种进入临床试验。说明用单一因子不能长效治疗阴茎血管病变。我们在前期研究中发现脂肪干细胞比骨髓细胞有更高的血管再生能力，并首次用其在糖尿病小鼠ED模型中诱导阴茎血管再生。在高脂血症小鼠ED模型中，阴茎内注射腺病毒-Comp-Angiopoietin-1或其蛋白质，使勃起能力恢复至注射后8周。本课题旨在结合多种方法（脂肪干细胞/ Comp-Angiopoietin-1基因或蛋白质）开发高效的血管再生技术，长效治疗ED。

糖尿病性勃起功能障碍(ED)患者对口服磷酸二酯酶5抑制剂的反应较差。因此，糖尿病性ED需要功能性治疗。脂肪基质血管成分(SVF)和腺病毒介导的COMP-Ang-1 (Ad - COMP - Ang1)基因在阴茎勃起中起重要作用。我们之前报道过SVF和Ad - COMP - Ang1单独应用在恢复勃起功能方面只有短期作用。我们有必要开发长效治疗勃起功能障碍的方法。 .在本研究中，我们的目的是测试SVF和Ad - COMP - Ang1的联用是否可以长效改善糖尿病性勃起功能障碍患者的勃起功能。我们发现联合治疗在恢复勃起功能方面有长期的效果。主要通过增强阴茎内皮和神经细胞再生。SVF与Ad - COMP - Ang1联合治疗明显恢复阴茎海绵体内皮细胞数量，周细胞数量，内皮细胞-细胞紧密连接蛋白含量，减少阴茎海绵体内皮细胞通透性，促进糖尿病小鼠神经再生至少达4周。.总之，SVF和Ad - COMP - Ang1联合治疗可长期恢复糖尿病性ED的勃起功能.是通过对阴茎海绵体内皮细胞和神经细胞再生的双重作用。这种联合治疗可能对于糖尿病性ED的治疗具有较好的前景。