用脂肪组织源性干细胞治疗肥胖 2 型糖尿病 ZDF 大鼠的勃起功能障碍。
Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells.
机构信息
Department of Urology, University of California School of Medicine-Knuppe Molecular Urology Laboratory, San Francisco, CA 94143-0738, USA.
出版信息
J Sex Med. 2010 Jan;7(1 Pt 1):89-98. doi: 10.1111/j.1743-6109.2009.01541.x.
INTRODUCTION
Erectile dysfunction (ED) is a major complication of type 2 diabetes, and many diabetic men with ED are refractory to common ED therapies.
AIM
To determine whether autologous adipose tissue-derived stem cells (ADSCs) injected into the penis of impotent type 2 diabetic rats improve erectile function.
MAIN OUTCOME MEASURES
Blood glucose levels, intracavernous pressure (ICP) increase upon cavernous nerve (CN) electrostimulation, and immunohistochemistry.
METHODS
Twenty-two male Zucker diabetic fatty (ZDF) rats were used. At 22 weeks of age, all the animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence. Paragonadal adipose tissue was harvested to procure ADSCs. The impotent animals were randomized to ADSC treatment and sham control groups. At 23 weeks of age, the treatment group animals underwent a penile injection of 1 million ADSCs; the control group animals received vehicle only. Erectile function studies were repeated at 26 weeks of age, followed by tissue harvest.
RESULTS
The rats developed diabetes within the first 10 weeks of age. At 22 weeks of age, 20 out of the 22 rats presented with ED. The post-treatment ICP increase during CN stimulation and ICP increase/mean arterial pressure were significantly higher in the treatment group compared with controls. Three weeks after injection into the corpus cavernosum, only a small number of BrdU-labeled ADSCs was detectable within corporal tissue of the treatment group. There was a significant increase in neuronal nitric oxide synthase (nNOS) in the penile dorsal nerve and in the number of endothelial cells in the corpora cavernosa of the rats in the treatment group.
CONCLUSION
Autologous ADSCs injected into the penis were effective to improve erectile function and to alter the microarchitecture of the corpus cavernosum. Since the number of ADSCs retained in the corpus cavernosum is very small, we postulate that their paracrine function, not trans-differentiation to smooth muscle or endothelial cells, is responsible for the improvement in penile function.
介绍
勃起功能障碍（ED）是 2 型糖尿病的主要并发症，许多患有 ED 的糖尿病男性对常见的 ED 治疗方法无反应。
目的
确定将自体脂肪组织源性干细胞（ADSCs）注射到勃起功能障碍的 2 型糖尿病大鼠阴茎中是否能改善勃起功能。
主要观察指标
血糖水平、海绵体内神经（CN）电刺激时的海绵体压（ICP）增加和免疫组织化学。
方法
使用 22 只雄性 Zucker 糖尿病肥胖（ZDF）大鼠。在 22 周龄时，所有动物均进行单侧 CN 电刺激和 ICP 测量以确认勃起功能障碍。采集旁睾脂肪组织以获取 ADSCs。将勃起功能障碍的动物随机分为 ADSC 治疗组和假手术对照组。在 23 周龄时，治疗组动物接受 100 万个 ADSC 的阴茎注射；对照组动物仅接受载体。在 26 周龄时重复进行勃起功能研究，然后进行组织采集。
结果
大鼠在出生后 10 周内就出现糖尿病。在 22 周龄时，22 只大鼠中有 20 只出现 ED。治疗组在 CN 刺激时的治疗后 ICP 增加和 ICP 增加/平均动脉压明显高于对照组。在将 BrdU 标记的 ADSC 注射到海绵体后 3 周，仅在治疗组的海绵体组织中可检测到少量的 BrdU 标记的 ADSC。治疗组大鼠阴茎背神经中的神经元型一氧化氮合酶（nNOS）和海绵体中的内皮细胞数量显著增加。
结论
将自体 ADSC 注射到阴茎中可有效改善勃起功能，并改变海绵体的微观结构。由于保留在海绵体中的 ADSC 数量非常少，我们推测它们的旁分泌功能，而不是向平滑肌或内皮细胞的转分化，是改善阴茎功能的原因。
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