Adrenomedullin Mediates Adipose Tissue-Derived Stem Cell-induced Restoration of Erectile Function in Diabetic Rats
Adrenomedullin Mediates Adipose Tissue-Derived Stem Cell-induced Restoration of Erectile Function in Diabetic Rats
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DOI：
10.1111/j.1743-6109.2011.02469.x
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发表时间：
2012-02-01
影响因子：
3.5
通讯作者：
Homma, Yukio
中科院分区：
文献类型：
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作者：
Nishimatsu, Hiroaki;Suzuki, Etsu;Homma, Yukio
导言。勃起功能障碍(ED)是一个主要的健康问题。众所周知，糖尿病患者对常见的ED治疗方法更难治。为了探索更好的治疗ED的方法，我们在糖尿病大鼠模型上检测了脂肪干细胞(ASC)对ED的影响。我们还分析了ASC产生的与ASC诱导的勃起功能恢复有关的细胞因子。雄性Wistar大鼠注射链脲佐菌素(STZ)复制糖尿病模型。注射STZ后6周，阴茎内注射ASC或腺病毒。在注射ASC或腺病毒4周后，分析勃起功能、阴茎组织学和蛋白表达。测量海绵体内压和平均动脉压以评估勃起功能。用Elastica van Gieson染色和免疫组织化学方法分析阴茎的形态。Western印迹分析血管内皮细胞(VEC)特异性蛋白的表达。ASC恢复勃起功能，尤其是在含有VEC生长因子的培养液中培养时。这种修复与海绵体组织学的改善以及VEC标志物如VE-钙粘素和内皮型一氧化氮合酶(ENOS)的表达增加有关。肾上腺髓质素(AM)是一种来源于人嗜铬细胞瘤组织的血管活性多肽，当其表达下调时，ASC对ED的作用明显减弱。AM表达下调与VE-cadherin和eNOS表达降低有关。此外，腺病毒感染诱导的AM过表达显著改善了这些糖尿病大鼠的勃起功能。AM的过度表达与VE-cadherin和eNOS的表达增加有关。这些结果提示ASC具有恢复勃起功能的潜能，ASC产生的AM在勃起功能的恢复中起主要作用。Nishimatsu H，Suzuki E，Kumano S，Nomiya A，Liu M，Kume H和Homma Y。肾上腺髓质素介导脂肪组织来源的干细胞诱导的糖尿病大鼠勃起功能的恢复。J Sex Med 2012；9：482-493。
Introduction. Erectile dysfunction (ED) is a major health problem. It is known that diabetic patients are more refractory to common treatments for ED.Aim. To explore the better treatment for ED, we examined the effects of adipose-derived stem cells (ASC) on ED using a diabetic rat model. We also analyzed the cytokines produced by ASC and implicated in ASC-induced restoration of erectile function.Methods. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. ASC or adenoviruses were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology and protein expression were analyzed 4 weeks after the injection of ASC or adenoviruses.Main Outcome Measures. Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of proteins specific for vascular endothelial cells (VEC) was assessed by Western blot analysis.Results. ASC restored erectile function especially when they were cultured in medium containing growth factors for VEC. This restoration was associated with improvement in the histology of the cavernous body, and increased expression of VEC markers such as VE-cadherin and endothelial nitric oxide synthase (eNOS). When the expression of adrenomedullin (AM), a vasoactive peptide originally isolated from human pheochromocytoma tissue, was knocked down, the effect of ASC on ED was significantly diminished. Knockdown of AM was associated with decreased expressions of VE-cadherin and eNOS. Furthermore, overexpression of AM induced by adenovirus infection significantly improved erectile function in these diabetic rats. Overexpression of AM was associated with increased expressions of VE-cadherin and eNOS.Conclusions. These results suggested that ASC have the potentials to restore erectile function and that AM produced by ASC plays a major role in the restoration of erectile function. Nishimatsu H, Suzuki E, Kumano S, Nomiya A, Liu M, Kume H, and Homma Y. Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats. J Sex Med 2012; 9: 482-493.