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低雄激素状态通过诱导大鼠海绵体中内皮型一氧化氮合酶解偶联来抑制勃起功能。

Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum.

作者信息

Xiong Wenju, Kong Xiangjun, Jiang Jun, Yang Zhihui, Jiang Rui

机构信息

Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

Department of Thyroid Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

出版信息

Andrology. 2020 Nov;8(6):1875-1883. doi: 10.1111/andr.12844. Epub 2020 Jul 12.

DOI:10.1111/andr.12844
PMID:32594586
Abstract

BACKGROUND

The number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology.

OBJECTIVES

To investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling.

MATERIALS AND METHODS

Thirty-six 8-week-old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4-week sham-operated group (4w-sham), 4-week castration group (4w-cast), 4-week castration + testosterone (T) group (4w-cast + T), 8-week sham-operated group (8w-sham), 8-week castration group (8w-cast), and 8-week castration + T group (8w-cast + T). Three mg/kg of T was subcutaneously injected every other day in castration + T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH ), tetrahydrobiopterin (BH ), nitric oxygen(NO), 3-nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected.

RESULTS

The ratio of ICPmax/MAP and BH /BH , the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham-operated groups and castration + T groups (P < .05) and decreased significantly in 8w-cast group compared with 4w-cast group (P < .05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham-operated groups and castration + T groups (P < .01) and increased significantly in 8w-cast group compared with 4w-cast group (P < .01). The expression of DHFR in 4w-cast group was significantly higher than that in 4w-sham group and 4w-cast + T group (P < .01) and in 8w-cast group was significantly lower than that in 8w-sham group and 8w-cast + T group (P < .01).

DISCUSSION AND CONCLUSION

Low androgen status induces eNOS uncoupling by reducing BH /BH and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.

摘要

背景

勃起功能障碍(ED)患者数量逐年增加。如何提高ED治疗效果是男科领域的重要问题。

目的

研究低雄激素状态是否通过调节内皮型一氧化氮合酶(eNOS)解偶联损害大鼠勃起功能。

材料与方法

将36只8周龄雄性Sprague Dawley(SD)大鼠随机分为6组:4周假手术组(4w-sham)、4周去势组(4w-cast)、4周去势+睾酮(T)组(4w-cast+T)、8周假手术组(8w-sham)、8周去势组(8w-cast)和8周去势+T组(8w-cast+T)。去势+T组每隔一天皮下注射3mg/kg的T。检测阴茎海绵体内最大压力/平均动脉压(ICPmax/MAP)比值、血清T、二氢生物蝶呤(BH)、四氢生物蝶呤(BH)、一氧化氮(NO)、3-硝基酪氨酸(3NT)、二氢叶酸还原酶(DHFR)、鸟苷三磷酸环化水解酶1(GTPCH1)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)水平以及阴茎海绵体内eNOS单体/二聚体比例。

结果

与假手术组和去势+T组相比,去势组的ICPmax/MAP比值、BH/BH、血清T、NO和GTPCH1水平显著降低(P<.05),且8w-cast组较4w-cast组显著降低(P<.05)。与假手术组和去势+T组相比,去势组3NT和NOX2表达以及eNOS单体/二聚体比例显著升高(P<.01),且8w-cast组较4w-cast组显著升高(P<.01)。4w-cast组DHFR表达显著高于4w-sham组和4w-cast+T组(P<.01),8w-cast组DHFR表达显著低于8w-sham组和8w-cast+T组(P<.01)。

讨论与结论

低雄激素状态通过降低BH/BH和增加3NT诱导eNOS解偶联。由于NO生成减少,大鼠勃起功能受损。

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