Further evidence of endogenous hydrogen sulphide as a mediator of relaxation in human and rat bladder

Further evidence of endogenous hydrogen sulphide as a mediator of relaxation in human and rat bladder
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DOI:
10.1038/aja.2013.32
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发表时间:
2013-09-01
影响因子:
2.9
通讯作者:
Jin, Jie
Jin, Jie
中科院分区:
医学2区
文献类型:
--
作者:
Gai, Jun-Wei;Wahafu, Wasilijiang;Jin, Jie

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我们研究了硫化氢 (H2S) 在人和大鼠下尿路(包括膀胱、前列腺和尿道)组织中的表达,并试图确定 H2S 是否会诱导人和 Sprague-Dawley (SD) 大鼠膀胱条松弛。获取人正常下尿路组织,使用硫化物敏感电极评估内源性 H2S 生产力,并通过蛋白质印迹法分析内源性 H2S 的所有三种合成酶:胱硫醚β-合酶(CBS)、胱硫醚γ裂解酶(CSE)和 3-巯基丙酮酸硫转移酶(MPST,称为 3-MST)的表达水平。通过免疫组织化学在人类样本载玻片中定位 CBS、CSE 和 MPST。使用传感器测试人类和雄性成年 SD 大鼠膀胱条的 H2S 功能并进行记录。所有实验重复六次。内源性 H2S 生产力和 H2S 合酶在人和大鼠下尿路组织中具有不同的分布,并且位于上皮和基质部分。 L-半胱氨酸(L-Cys,CBS、CSE 和 MPST 的底物)以剂量依赖性方式对氯化乙酰胆碱预收缩的人膀胱条产生松弛。 ATP 敏感的钾离子 (K-ATP) 通道阻滞剂格列本脲 (GLB)、CSE 抑制剂 DL-炔丙基甘氨酸 (PPG) 和 CBS 抑制剂羟胺 (HA) 可以减弱这种效应。 H2S及其三种合酶存在于人和大鼠下尿路组织以及松弛的人和大鼠膀胱条中,这表明内源性H2S可能在下尿路症状(LUTS)或膀胱过度活动症(OAB)的生理功能和病理紊乱中发挥作用。
We investigated the expression of hydrogen sulphide (H2S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley (SD) rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine beta-synthase (CBS), cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulphur transferase (MPST, as known as 3-MST) by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine (L-Cys, a substrate of CBS, CSE and MPST) elicited relaxation in a dose-dependent manner on human bladder strips pre-contracted by acetylcholine chloride. This effect could be diminished by the ATP-sensitive potassium ion (K-ATP) channel blocker glibenclamide (GLB), the CSE inhibitor DL-propargylglycine (PPG) and the CBS inhibitor hydroxylamine (HA). H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms (LUTS) or overactive bladder (OAB).