Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide
Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide
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DOI：
10.1155/2019/5641645
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发表时间：
2019-08-20
影响因子：
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通讯作者：
Hernandez, Medardo
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文献类型：
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作者：
Blaha, Igor;Elvira Lopez-Oliva, Maria;Hernandez, Medardo
目的。本研究探讨了瞬时受体电位香草酸 1 (TRPA1) 和瞬时受体电位锚蛋白 1 (TRPA1) 通道的功能和/或表达变化、氧化应激和硫化氢 (H2S) 是否与胰岛素抵抗肥胖 Zucker 大鼠 (OZR) 的膀胱功能障碍有关。材料和方法。对来自 OZR 及其各自对照瘦 Zucker 大鼠 (LZR) 的逼尿肌平滑肌 (DSM) 样本进行免疫组织化学处理，以研究 TRPA1 和 TRPV1 以及 H2S 合酶胱硫醚 β 合酶 (CBS) 和胱硫醚-γ-裂解酶 (CSE) 的表达。还进行了等长力记录，以评估 TRPA1 激动剂和拮抗剂对 DSM 收缩性的影响，并测量氧化应激和 H2S 产生。结果。 OZR 膀胱中神经元 TRPA1 表达增加。电场刺激（EFS）引起的 OZR 膀胱收缩减少。在 LZR 和 OZR 中，TRPA1 激活未能改变 DSM 基础张力，但增强了 EFS 收缩；这种反应被 TRPA1 阻断所抑制。在OZR膀胱中，活性氧、丙二醛和蛋白质羰基含量增加，抗氧化酶活性（超氧化物歧化酶、过氧化氢酶、GR和GPx）减少。 OZR 中的 ca 表达和 CSE 产生的 H2S 产量也有所减少。 OZR 中 TRPV1 和 CBS 表达均未改变。结论。这些结果表明，TRPA1 表达和功能的增加、氧化应激的增强以及 CSE/H2S 通路的下调与 OZR 神经诱发的 DSM 收缩的损害有关。
Purpose. This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPA1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods. Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-gamma-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results. Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. ca expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions. These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.