Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats
Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats
复制标题
下调的 CBS/H2S 通路参与 Dahl 大鼠高盐诱导的高血压
DOI：
10.1016/j.niox.2015.01.004
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发表时间：
2015-04-30
影响因子：
3.9
通讯作者：
Jin, Hongfang
中科院分区：
文献类型：
--
作者：
Huang, Pan;Chen, Siyao;Jin, Hongfang
背景资料：为探讨内源性H2S在高盐性高血压大鼠发病中的意义，采用Dahl大鼠高盐饲料（含8%NaCl）喂养8周建立高盐性高血压大鼠模型，SD大鼠作为对照。观察大鼠收缩压和主动脉结构。检测肾组织内源性H2S含量及胱硫醚β-裂解酶（CBS）、胱硫醚γ-裂解酶和巯基丙酮酸硫转移酶的表达。以HIF-1 α通路为靶点，研究高盐对肾组织CBS/H2S的影响机制。结果：高盐可降低盐敏感Dahl大鼠肾组织内源性H2S含量，抑制CBS表达。然而，H2S供体可抑制Dahl大鼠的盐敏感性高血压，逆转主动脉结构重构，并抑制肾组织RAS系统的激活。在高盐饮食的Dahl大鼠肾组织中，HIF-1 α的表达降低，而PHD 2的表达增加，而在高盐饮食的SD大鼠肾组织中，它们没有改变。体外实验表明，HIF-1 α降解抑制剂可挽救高盐Dahl大鼠肾组织中下调的CBS/H2S通路。结论：高盐损伤下肾组织CBS/H2S通路表达下调可能是盐敏感性高血压的重要发病机制之一。(C)2015爱思唯尔公司All rights reserved.
Background: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats.Methods: High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine beta-lyase (CBS), cystathionine gamma-Iyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1 alpha pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested.Results: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1 alpha was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1 alpha degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1 alpha activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt.Conclusions: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension. (C) 2015 Elsevier Inc. All rights reserved.