Huang Pan, Chen Siyao, Wang Yuan, Liu Jia, Yao Qiuyu, Huang Yaqian, Li Hongxia, Zhu Mingzhu, Wang Suxia, Li Lin, Tang Chaoshu, Tao Yinghong, Yang Guosheng, Du Junbao, Jin Hongfang
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Lab of Electric Microscopy, Peking University First Hospital, Beijing 100034, China.
Nitric Oxide. 2015 Apr 30;46:192-203. doi: 10.1016/j.niox.2015.01.004. Epub 2015 Jan 21.
The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats.
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 β-lyase (CBS), cystathionine γ-lyase 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-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested.
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-1α 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-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt.
Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.
本研究旨在探讨内源性硫化氢（H2S）在大鼠高盐诱导高血压发生发展中的意义。
通过给Dahl大鼠喂食含8%氯化钠的高盐饮食8周建立高盐诱导高血压大鼠模型，以SD大鼠作为对照。观察大鼠的收缩压（SBP）和主动脉结构。检测肾组织中内源性H2S含量以及胱硫醚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。以缺氧诱导因子-1α（HIF-1α）途径为靶点，研究高盐对肾组织中CBS/H2S的影响机制。检测H2S对大鼠血清和肾组织中肾素-血管紧张素系统（RAS）的作用。
高盐降低了盐敏感型Dahl大鼠肾组织内源性H2S含量并抑制了CBS的表达。然而，H2S供体抑制了盐敏感型高血压，逆转了主动脉结构重塑，并抑制了Dahl大鼠肾组织中RAS系统的激活。高盐饮食的Dahl大鼠肾组织中HIF-1α表达降低，但脯氨酰羟化酶2（PHD2）表达增加，而高盐饮食的SD大鼠肾组织中这些指标未发生改变。体外实验表明，HIF-1α降解抑制剂可挽救高盐处理的Dahl大鼠肾组织中下调的CBS/H2S途径。相反，HIF-1α活性抑制剂降低了高盐处理的SD大鼠肾组织中的CBS/H2S途径。
高盐刺激下肾组织中CBS/H2S途径下调可能是盐敏感型高血压的重要发病机制。
