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糖尿病性勃起功能障碍大鼠阴茎组织中内源性硫化氢生成减少。

Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.

作者信息

Zhang Yan, Yang Jun, Wang Tao, Wang Shao-Gang, Liu Ji-Hong, Yin Chun-Ping, Ye Zhang-Qun

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

J Sex Med. 2016 Mar;13(3):350-60. doi: 10.1016/j.jsxm.2016.01.002. Epub 2016 Feb 4.

DOI:10.1016/j.jsxm.2016.01.002
PMID:26853047
Abstract

INTRODUCTION

Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats.

METHODS

Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition.

MAIN OUTCOME MEASURES

Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs.

RESULTS

Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S-generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group.

CONCLUSION

Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE.

摘要

引言

硫化氢(H2S)是一种内源性气体递质。患有勃起功能障碍(ED)的糖尿病大鼠中,产生H2S的酶表达水平和内源性H2S产量仍不清楚。本研究的目的是调查糖尿病性ED大鼠阴茎组织中产生H2S的酶的表达及内源性H2S的产生情况。

方法

将实验大鼠随机分为正常对照组、阿扑吗啡(APO)阳性组和APO阴性组。原代大鼠海绵体平滑肌细胞(CCSMC)和主动脉内皮细胞(AEC)在3种不同条件下进行体外分离和培养:正常葡萄糖(NG)条件、高葡萄糖(HG)条件和渗透对照(OC)条件。

主要观察指标

勃起功能;血浆或阴茎组织中的H2S浓度;阴茎组织、CCSMC和AEC中产生H2S的酶的表达及内源性H2S的产生。

结果

APO阴性组的勃起功能显著降低。除了半胱氨酸转氨酶(CAT)、D-氨基酸氧化酶(DAO)和3-巯基丙酮酸硫转移酶(3-MST)的表达显著降低外,APO阴性组血浆和阴茎组织中的H2S浓度以及内源性H2S产量也显著降低。APO阴性组和APO阳性组中,由胱硫醚β-合酶(CBS)和胱硫醚γ-裂合酶(CSE)产生的内源性H2S降至与正常对照组相同的水平。然而,CBS和CSE的表达在3组中保持不变。在HG条件下,AEC中产生H2S的酶的表达没有变化,而CCSMC中CAT、DAO和3-MST的表达显著降低。在两种细胞类型中,HG组中这些酶产生的H2S均减少。

结论

由于CAT/3-MST和DAO/3-MST途径的表达下调以及CBS和CSE的活性较低,糖尿病性ED大鼠阴茎组织中的内源性H2S产生显著减少。

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