Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.
Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.
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DOI：
10.1016/j.jsxm.2016.01.002
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Yan Zhang;Jun Yang;Tao Wang;Shaogang Wang;Ji-Hong Liu;C. Yin;Z. Ye
中科院分区：
文献类型：
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作者：
Yan Zhang;Jun Yang;Tao Wang;Shaogang Wang;Ji-Hong Liu;C. Yin;Z. Ye
硫化氢(H_2S)是一种内源性气体递质。糖尿病合并勃起功能障碍(ED)大鼠的H_2S生成酶表达水平和内源性H_2S产生水平尚不清楚。本研究旨在探讨糖尿病ED大鼠阴茎组织中H_2S生成酶的表达及内源性H_2S的产生。方法实验大鼠随机分为正常对照组、阿朴吗啡(APO)阳性组和APO阴性组。分离原代培养的大鼠阴茎海绵体平滑肌细胞(CCSMCs)和主动脉内皮细胞(AECs)，在正常糖(NG)、高糖(HG)和渗透压对照(OC)条件下进行体外培养。主要观察指标：勃起功能；血浆和阴茎组织中H_2S浓度；阴茎组织、CCSMCs和AEC中H_2S生成酶的表达和内源性H_2S的产生。APO阴性组除了半胱氨酸氨基转移酶(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，血浆和阴茎组织中的H_2S浓度和内源性H_2S的生成量也显著减少。硫代半胱氨酸β合酶和γ裂解酶产生的内源性H_2S在APO阴性和APO阳性组降低到与正常对照组相同的水平。而CBS和CSE在3组中的表达无明显变化。在HG条件下，血管内皮细胞H_2S产生酶的表达无明显变化，而CAT、DAO和3-MST的表达显著降低。结论糖尿病ED大鼠阴茎组织内源性硫化氢生成显著减少，其原因是CAT/3-MST和DAO/3-MST途径表达下调，CBS和CSE活性降低。
IntroductionHydrogen 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.MethodsExperimental 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 MeasuresErectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs.ResultsErectile 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.ConclusionEndogenous 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.