The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.
The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.
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DOI：
10.1111/j.1743-6109.2009.01697.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Lin CS
中科院分区：
文献类型：
--
作者：
Huang YC;Ning H;Shindel AW;Fandel TM;Lin G;Harraz AM;Lue TF;Lin CS
高脂血症与勃起功能障碍(ED)有关，它通过损伤海绵体内皮细胞和神经而发生。脂肪组织来源的干细胞(ADSC)可以分化为内皮细胞，并分泌血管营养因子和神经营养因子。目的：评价ADSC对高脂血症相关性ED的治疗作用。用高脂饲料诱导28只雄性大鼠形成高脂血症模型(高脂血症大鼠，HR)。另外10只雄性大鼠以正常饲料喂养作为对照组(正常大鼠，NR)。5个月后，所有大鼠接受ADSC分离，分离出副肾上腺脂肪。培养1周，5-乙炔基-2‘-脱氧尿苷(EDU)标记后，自体注射入18只HR的海绵体内。其余10只大鼠注射磷酸盐缓冲液(PBS)。分别于移植后3d和14d处死HR+ADSC组大鼠4只，追踪移植细胞。移植后1个月，对其余大鼠进行血清生化、勃起功能和阴茎组织学检查。电刺激海绵体神经时，通过测量海绵体内压力来评估勃起功能。免疫组织化学方法检测海绵体神经、血管内皮细胞和血管内皮细胞。HR组血清总胆固醇和低密度脂蛋白水平显著高于NR组。HR组高密度脂蛋白水平显著低于NR组。HR+PBS组平均海绵体内压/平均动脉压比值显著低于NR+PBS组和HR+ADSC组。HR+PBS组神经元型一氧化氮合酶(NNOS)阳性神经纤维和内皮细胞较HR+ADSC组少。两个HR组的血管平滑肌含量均显著高于正常对照组。高脂血症与神经和内皮的异常有关。ADSC治疗可改善这些不良反应，有望成为治疗ED的潜在新疗法。
Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Twenty-eight male rats were induced to develop hyperlipidemia with a high fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for one week, labeled with 5-ethynyl-2′-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate-buffered saline (PBS). At 3 and 14 days post-transplantation, 4 rats in the HR+ADSC group were sacrificed for tracking of the transplanted cells. At one month post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function and penile histology. Erectile function was assessed by intracavernous pressure measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean intracavernous pressure/mean arterial pressure ratio was significantly lower in HR+PBS than in NR+PBS or HR+ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR+PBS than in HR+ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.
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