Nitric oxide synthase gene transfer for erectile dysfunction in a rat model
Nitric oxide synthase gene transfer for erectile dysfunction in a rat model
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DOI：
10.1046/j.1464-410x.2003.04219.x
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发表时间：
2003-05-01
影响因子：
4.5
通讯作者：
Yoshimura, N
中科院分区：
文献类型：
--
作者：
Chancellor, MB;Tirney, S;Yoshimura, N
目的探讨一氧化氮合酶（NO）在阴茎海绵体中的过表达是否能改善勃起功能，因为NO是泌尿生殖道功能的重要递质，介导平滑肌松弛，对阴茎勃起至关重要。材料与方法采用质粒、腺病毒或腺病毒介导的成肌细胞（adeno-myoblasts, adeno-myoblasts）溶液注入成年spraguedawley大鼠海绵体（250 ~ 300 g），诱导型NOS （iNOS）酶。将编码-半乳糖苷酶报告基因表达的质粒、腺病毒和腺成肌细胞注射到大鼠体内。结果三种溶液注射后海绵体均有β -半乳糖苷酶的表达。腺成肌细胞染色最大，腺病毒次之，质粒染色最大。inos处理动物（腺病毒和腺肌母细胞）的平均（sd）基础海膜内压（ICP）增加到55 (23)cmH(2) O，而未处理动物的基础ICP为5 (6)cmH(2) O （P = 0.001）。刺激海绵体神经（15 Hz, 1.5 ms, 10-40 V, 1 min）可使inos处理动物的ICP（腺病毒和腺成肌细胞）从基础水平增加一倍。直接原位测量NO，显示成腺肌细胞阴茎释放1-1.3 μ mol/L。结论成肌细胞介导的基因治疗比直接腺病毒注射或质粒转染更能成功地将iNOS送入海绵体。令人惊讶的是，将肌肉细胞植入阴茎不仅可行而且有益。NOS的基因治疗可能为治疗勃起功能障碍开辟新的途径。控制NOS表达是预防勃起功能障碍的必要措施。
OBJECTIVETo determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection.MATERIALS AND METHODSThe inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats.RESULTSThroughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH(2) O, compared with naive animals with a basal ICP of 5 (6) cmH(2) O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 mumol/L in the adeno-myoblast penis.CONCLUSIONMyoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.