Gene transfer of extracellular SOD to the penis reduces O2-. and improves erectile function in aged rats
Gene transfer of extracellular SOD to the penis reduces O2-. and improves erectile function in aged rats
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DOI：
10.1152/ajpheart.00770.2002
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发表时间：
2003-04-01
影响因子：
4.8
通讯作者：
Champion, HC
中科院分区：
文献类型：
--
作者：
Bivalacqua, TJ;Armstrong, JS;Champion, HC
超氧阴离子（O-2(-.)）增加可能导致衰老过程中的血管功能障碍。在老化的海绵体组织中，光泽精增强的化学发光显示超氧化物的形成增加了三倍，氧化荧光探针氢乙啶表明整个老化阴茎的超氧化物水平较高。超氧化物的增加与海绵体神经介导和激动剂诱导的勃起反应受损、硝基酪氨酸染色增加和 cGMP 水平降低有关，但海绵体细胞外 (EC)-超氧化物歧化酶 (EC-SOD) mRNA 或蛋白质没有代偿性变化。 EC-SOD 的体内腺病毒 (Ad) 基因转移到阴茎导致 EC-SOD mRNA、蛋白质、SOD 活性、cGMP 水平更高的表达，以及更低的硝基酪氨酸染色。 AdCMVEC-SOD 转染导致对海绵体神经刺激、ACh 和扎普司特的勃起反应显着增加，其程度与年轻大鼠相似。这些数据提供了支持以下假设的证据：与衰老相关的勃起功能障碍部分与海绵体 O-2 形成的增加有关。 EC-SOD 的基因转移减少了超氧化物的形成并恢复与年龄相关的勃起功能，并且可能代表治疗勃起功能障碍的新治疗靶点。
Increased superoxide anion (O-2(-.)) may contribute to vascular dysfunction in aging. In aged cavernosal tissue, lucigenin-enhanced chemiluminescence demonstrated a threefold increase in superoxide formation, and the oxidative fluorescent probe hydroethidine indicated higher superoxide levels throughout the aged penis. This increase in superoxide was associated with impaired cavernosal nerve-mediated and agonist-induced erectile responses, increased nitrotyrosine staining, and lower cGMP levels, but no compensatory change in cavernosal extracellular (EC)-superoxide dismutase (EC-SOD) mRNA or protein. In vivo adenoviral (Ad) gene transfer of EC-SOD to the penis resulted in higher expression of EC-SOD mRNA, protein, SOD activity, cGMP levels, and lower nitrotyrosine staining. Transfection with AdCMVEC-SOD resulted in a significant increase in erectile response to cavernosal nerve stimulation, ACh, and zaprinast to a magnitude similar to young rats. These data provide evidence in support of the hypothesis that erectile dysfunction associated with aging is related in part to an increase in cavernosal O-2 formation. Gene-transfer of EC-SOD reduces superoxide formation and restores age-associated erectile function and may represent a novel therapeutic target for the treatment of erectile dysfunction.