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长期口服精氨酸酶抑制剂2(S)-氨基-6-硼己酸(ABH)可改善老年大鼠的勃起功能。

Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats.

作者信息

Segal Robert, Hannan Johanna L, Liu Xiaopu, Kutlu Omer, Burnett Arthur L, Champion Hunter C, Kim Jae Hyung, Steppan Jochen, Berkowitz Dan E, Bivalacqua Trinity J

机构信息

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins MedicalInstitutions, Baltimore, Maryland, USA.

出版信息

J Androl. 2012 Nov-Dec;33(6):1169-75. doi: 10.2164/jandrol.111.015834. Epub 2012 Apr 5.

Abstract

Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function.

摘要

精氨酸酶的表达和活性在与勃起功能障碍相关的情况下会升高,包括衰老。此前,长期给予精氨酸酶抑制剂2-(S)-氨基-6-硼己酸(ABH)已被证明可改善老年大鼠的内皮功能障碍。本研究的目的是评估长期口服ABH是否会影响海绵体勃起功能。将大鼠分为4组:年轻对照组、用精氨酸酶抑制剂治疗的年轻组、老年对照组和用精氨酸酶抑制剂治疗的老年组。测量精氨酸酶活性,并以未治疗的年轻大鼠的比例表示。在所有组中测量对海绵体神经刺激的体内勃起反应。用分级电刺激刺激海绵体神经,并记录海绵体内/平均动脉压比值和海绵体内总压力。与年轻对照组相比,老年大鼠的精氨酸酶活性升高;然而,用ABH治疗的老年大鼠的精氨酸酶活性显著降低。添加ABH后,老年大鼠的勃起反应有所改善(P <.05)。用ABH口服抑制精氨酸酶可改善老年大鼠的勃起功能,使勃起血流动力学类似于年轻大鼠。这是系统性精氨酸酶抑制对海绵体功能产生积极影响的首次记录。

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