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脂肪来源干细胞和 BDNF 固定化 PLGA 膜在大鼠海绵体神经损伤模型中的治疗效果。

Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury.

机构信息

Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

J Sex Med. 2012 Aug;9(8):1968-79. doi: 10.1111/j.1743-6109.2012.02760.x. Epub 2012 May 29.

Abstract

INTRODUCTION

Cavernous nerve injury is the main reason for post-prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED.

AIM

To evaluate the therapeutic efficacy of adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF) immobilized Poly-Lactic-Co-Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post-prostatectomy ED. Methods.  Rats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF-membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF-membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled-released for a period of 4 weeks in a BDNF/PLGA porous membrane system.

MAIN OUTCOME MEASURES

Four weeks after the operation, erectile function was assessed by detecting the ratio of intra-cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho-endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively.

RESULTS

In the ADSC/BDNF-membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF-membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups.

CONCLUSIONS

ADSCs with BDNF-membrane on the cavernous nerve can improve erectile function in a rat model of post-prostatectomy ED, which may be used as a novel therapy for post-prostatectomy ED.

摘要

简介

海绵体神经损伤是前列腺切除术后勃起功能障碍(ED)的主要原因。干细胞和神经保护疗法是 ED 的一种很有前途的治疗策略。

目的

评估聚乳酸-共-羟基乙酸(PLGA)膜固定脂肪来源干细胞(ADSCs)和脑源性神经营养因子(BDNF)对前列腺切除术后 ED 大鼠模型海绵体神经的治疗效果。方法。大鼠随机分为五组:正常组、双侧海绵体神经挤压损伤(BCNI)组、ADSC(BCNI 组海绵体神经上有 ADSCs)组、BDNF 膜(BCNI 组海绵体神经上有 BDNF/PLGA 膜)组和 ADSC/BDNF 膜(BCNI 组海绵体神经上有 ADSCs 覆盖 BDNF/PLGA 膜)组。BDNF 在 BDNF/PLGA 多孔膜系统中控制释放 4 周。

主要观察指标

术后 4 周,通过检测海绵体压(ICP)/平均动脉压(MAP)比值评估勃起功能。通过 Masson 三色染色法测定平滑肌和胶原含量。免疫染色检测阴茎背神经中神经元型一氧化氮合酶(nNOS)的表达。通过 Western blot 和 cGMP 测定分别定量测定海绵体磷酸化内皮型一氧化氮合酶(eNOS)蛋白表达和环鸟苷酸(cGMP)水平。

结果

ADSC/BDNF 膜组与 BCNI 组和其他治疗组相比,勃起功能明显提高。与 BCNI 组和其他治疗组相比,ADSC/BDNF 膜治疗组平滑肌/胶原比、nNOS 含量、磷酸化 eNOS 蛋白表达和 cGMP 水平显著增加。

结论

在前列腺切除术后 ED 大鼠模型中,BDNF 膜固定在海绵体神经上的 ADSC 可改善勃起功能,可能成为前列腺切除术后 ED 的一种新的治疗方法。

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