骨髓间充质干细胞即刻与延时治疗修复阴茎海绵体神经损伤大鼠勃起功能的研究  

Immediate and delayed intracavernous injection of bone marrow mesenchymal stem cells to improve erectile function in rats with cavernous nerve injury

作　　者：孙超[1] 朱伟东[1] 柳靖[1] 姜华[1] 陈明[1] 张晓毅[1] SUN Chao ZHU Wei-dong LIU Jing JIANG Hua CHEN Ming(Department of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, China)

机构地区：[1]东南大学附属中大医院泌尿外科,江苏南京210009

出　　处：《中华男科学杂志》2017年第5期392-398,共7页National Journal of Andrology

基　　金：国家自然科学基金(81300472)~~

摘　　要：目的:拟观察在双侧阴茎海绵体神经(CN)损伤的大鼠神经性勃起功能障碍(NED)模型中即刻和延时向阴茎海绵体注射骨髓间充质干细胞(BM-MSCs)对大鼠阴茎勃起功能的修复作用。方法:选取28只8周龄、体重200~250 g雄性SD大鼠随机分为4组:假手术组找到双侧海绵体神经后不做处理直接关腹并缝合皮肤;对照组、即刻治疗组和延时治疗组均通过钳夹的方式损伤双侧阴茎海绵体神经建立NED模型随后关腹缝合。假手术组和对照组向阴茎海绵体内注射对照剂,即刻治疗组注射BM-MSCs,延时治疗组术后两周注射BM-MSCs。术后12周采用电刺激CN记录阴茎海绵体内压(ICP),颈动脉穿刺测定平均动脉压(MAP),ICP/MAP作为勃起功能的评价指标来评估大鼠的勃起功能。在勃起功能检测后处死大鼠,取阴茎海绵体中段组织检测平滑肌、胶原和神经纤维。结果:在手术后12周,即刻治疗组和延时治疗组ICP和ICP/MAP均较对照组升高(P<0.05)。即刻治疗组和延时治疗能提高大鼠海绵体组织内平滑肌与胶原的比例(P<0.05),同时两组阴茎海绵体内平滑肌含量高于对照组(P<0.05),阴茎海绵体背神经内神经微丝(NF)蛋白阳性神经纤维数目和nNOS的表达高于对照组(P<0.05)。结论:阴茎海绵体内注射BM-MSCs能对双侧CN损伤大鼠的勃起功能恢复有促进作用。BM-MSCs治疗可以提高海绵体组织内平滑肌与胶原的比例,改善纤维化,并能提高海绵体组织中平滑肌含量、阴茎背神经的神经丝含量和nNOS的表达水平,术后延时治疗同样能取得一定的治疗效果。Objective： To explore the effects of immediate and delayed intracavernous injection of bone marrow mesenchymal stem cells （BM-MSCs） on neurogenic erectile dysfunction （NED） induced by bilateral cavernous nerve injury in Sprague-Dawley （SD） rats. Methods ： BM-MSCs isolated from male SD rats were cultured and identified. Twenty-eight 8-week-old male SD rats were randomly divided into four groups, sham operation, NED model control, BM-MSCs immediate, and BM-MSCs delayed, and NED models were established in the latter three groups by crushing the bilateral cavernous nerves. The rats in the sham operation and model control groups were injected intracavernously with placebo while those in the latter two with BM-MSCs immediately or 2 weeks after modeling. At 12 weeks after operation, the penile function of the rats was assessed according to the penile intracavernous pressure （ICP） , mean arterial pressure （MAP） , and ICP/MAP ratio obtained from different groups of rats. Then, all the animals were sacri- riced and the penile cavernosal tissue collected for histological analysis. Results： At 12 weeks after modeling, both ICP and ICP! MAP were significantly increased in the BM-MSCs immediate and delayed groups as compared with those in the model control （P 〈 0.05 ）, and so were the ratio of smooth muscle to collagen （ P 〈 0.05 ） and the smooth muscle content in the corpus cavernosum （ P 〈 0.05） , and the number of neurofilament （NF）-positive nerve fibers （P 〈 0.05） and the expression of neuronal nitric oxide synthase （nNOS） in the dorsal nerves of the midshaft penis （ P 〈0. 05 ）. Conclusion ： Intracavernous injection of BM-MSCs can improve erectile function in rats with bilateral cavernous nerve injury by elevating the smooth muscle-collagen ratio and smooth muscle content in the corpus cavernosum and thus preventing its fibrosis as well as by increasing the number of NF-positive nerve fibers and expression of nNOS in the penile dorsal nerves.

关 键 词：骨髓间充质干细胞 勃起功能障碍 海绵体神经 大鼠 

分 类 号：R698[医药卫生—泌尿科学]