Preserved Erectile Function in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1
Preserved Erectile Function in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1
复制标题
携带人体组织激肽释放酶 1 的老年转基因大鼠保留勃起功能
DOI：
10.1016/j.jsxm.2016.07.005
复制
发表时间：
2016-09-01
影响因子：
3.5
通讯作者：
Wang, Daowen
中科院分区：
文献类型：
--
作者：
Luan, Yang;Ruan, Yajun;Wang, Daowen
Introduction: Human tissue kallikrein 1 (hKLK1) has enormous potential for the protection of vasodilation and endothelial function in the cardiovascular system. Our previous study proved the decreased expression of kallikrein 1 in the corpus cavernosum (CC) of aged rats, but the role of kallikrein 1 in age-related erectile dysfunction remains unknown.Aim: To explore the effect and underlying mechanisms of hKLK1 on age-related erectile dysfunction.Methods: Male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 27 months of age, respectively, and divided into four groups: young WTR (yWTR) as the control, young TGR (yTGR), aged WTR (aWTR), and aged TGR (aTGR). Rats' erectile function was evaluated by the cavernous nerve electrostimulation method. Then, CCs were collected for verification of hKLK1 followed by measurement of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) and RhoA-Rho-kinase (ROCK) signaling activities. Masson trichrome staining and terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling assay were conducted to evaluate penile fibrosis and apoptosis.Main Outcome Measures: Erectile response, NO-cGMP and RhoA-ROCK pathway-related indices, ratio of smooth muscle to collagen, and apoptosis index.Results: The hKLK1 alleviated the decrease of erectile function in the aWTR group. Endothelial NO synthase (eNOS) and phospho-eNOS(Ser1177) expressions, NO synthase activity, and NO and cGMP levels were decreased, whereas phospho-eNOS(Thr495), L-type Ca2+ channel, RhoA, ROCK1, ROCK2, and transforming growth factor beta 1 proteins were increased in the CCs of the aWTR group compared with the control yWTR group. These changes were obviously mitigated in the aTGR group. Moreover, hKLK1 prevented the sharp decrease of the ratio of smooth muscle to collagen and the increase of the apoptosis index in the CCs of the aWTR group.Conclusion: These results suggest that hKLK1 could play a preventive role in age-related erectile dysfunction by activation of the NO-cGMP pathway and inhibition of the RhoA-ROCK pathway and by antitissue fibrotic and apoptotic effects. Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
