Abstract：
As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson\'s trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.
摘要：
作为前列腺癌的标准疗法，根治性前列腺切除术（RP）会导致海绵状神经损伤，并增加纤维化和缺氧引起的阴茎结构改变。这项研究旨在确定脂肪干细胞（ADSC）和L-精氨酸单独或组合对双侧海绵体神经（CN）横断引起的勃起功能障碍（ED）大鼠模型的阴茎勃起的潜在有益作用。雄性大鼠（n=35）随机分为五组：假手术；CN横切（4周）；CN横切加ADSCs（海绵体内注射1×106个细胞）；CN横切加L-精氨酸（4周，10毫克/千克/天，口服）；以及在CN横断中与L-精氨酸结合的ADSCs。测量体内勃起反应和体外松弛反应。Westernblot和免疫组化分析用于确定内皮一氧化氮合酶（eNOS）的表达和定位，神经元型NOS(nNOS),转化生长因子-β1（TGF-1），缺氧诱导因子-1(HIF-1),和凋亡标志物（Bax和Bcl-2）。使用Masson三色和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）-黄递酶染色计算平滑肌与胶原和神经再生的比率。联合治疗恢复了减少的勃起反应，内皮依赖性乙酰胆碱，和电场刺激诱导的CN横断大鼠阴茎海绵体松弛，而任一单一疗法仅产生部分改善。所有治疗方案均恢复了具有CN横断的啮齿动物中HIF-1和Bax蛋白表达的增加。单药治疗部分改善了平滑肌质量和NADPH-心肌黄递酶阳性神经纤维的减少，而联合治疗导致恢复。这些发现表明，ADSCs和L-精氨酸的联合治疗可以通过抑制缺氧诱导的神经毒性并保持内皮功能和平滑肌含量来恢复CN横断的啮齿动物的勃起功能。
