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脂肪组织源性干细胞治疗法在预防和治疗佩罗尼氏病大鼠模型勃起功能障碍中的应用。

Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie's disease.

机构信息

Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.

出版信息

Andrology. 2014 Mar;2(2):244-51. doi: 10.1111/j.2047-2927.2013.00181.x.

Abstract

Peyronie's disease (PD) is a localized connective tissue disorder that involves the tunica albuginea (TA) of the penis. While surgical correction remains the gold standard, the search for an effective and less invasive therapy continues. The objective of this study was to evaluate the effects of intratunical injection of adipose tissue-derived stem cells (ADSCs) for the prevention and treatment of erectile dysfunction in a rat model of PD. Twenty-four male Sprague-Dawley rats (300-350 g) were randomly divided into four groups: sham, PD, PD + ADSC (prevention) and PD + ADSC (treatment). All rats underwent penile injections into the TA with 50 μL vehicle (sham) or 0.5 μg transforming growth factor (TGF)-β1 (remaining groups). The ADSC groups received intratunical injections with 0.5 million rat-labelled ADSCs on day 0 (prevention) or day 30 (treatment). Forty-five days following TGF-β1 injection, rats underwent cavernous nerve stimulation (CNS) with total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP recorded to measure response to therapy. Tissues were evaluated histologically and for mRNA expression of tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs) and zymographic activity of MMPs. Statistical analysis was performed by analysis of variance followed by the Tukey test for post hoc comparisons. In both prevention and treatment groups, intratunical injection of ADSCs resulted in significantly higher ICP/MAP and total ICP in response to CNS compared with the PD group. Local injection of ADSCs prevented and/or reduced Peyronie's-like changes by decreasing the expression of TIMPs, and stimulating expression and activity of MMPs. This study documents the preventive and therapeutic benefits of ADSC on penile fibrosis and erectile function in an animal model of PD.

摘要

佩罗尼氏病(PD)是一种局部结缔组织疾病,涉及阴茎的白膜。虽然手术矫正仍然是金标准,但对有效且侵入性较小的治疗方法的研究仍在继续。本研究的目的是评估脂肪组织源性干细胞(ADSCs)在 PD 大鼠模型中预防和治疗勃起功能障碍的效果。24 只雄性 Sprague-Dawley 大鼠(300-350g)随机分为四组:假手术组、PD 组、PD+ADSC(预防)组和 PD+ADSC(治疗)组。所有大鼠的白膜内均注射 50μL 载体(假手术组)或 0.5μg 转化生长因子-β1(其余组)。ADSC 组在第 0 天(预防)或第 30 天(治疗)接受 0.5 百万个标记的 ADSC 白膜内注射。在 TGF-β1 注射后 45 天,大鼠接受海绵体神经刺激(CNS),记录总海绵体内压与平均动脉压比值(ICP/MAP)和总 ICP,以测量对治疗的反应。组织学评估和组织抑制剂金属蛋白酶(TIMPs)、基质金属蛋白酶(MMPs)的 mRNA 表达以及 MMPs 的酶谱活性。采用方差分析进行统计分析,然后采用 Tukey 检验进行事后比较。在预防和治疗组中,与 PD 组相比,ADSC 白膜内注射导致 CNS 反应时 ICP/MAP 和总 ICP 显著升高。局部注射 ADSC 通过降低 TIMPs 的表达,并刺激 MMPs 的表达和活性,预防和/或减少了 PD 样变化。本研究记录了 ADSC 在 PD 动物模型中对阴茎纤维化和勃起功能的预防和治疗作用。

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