Sulfur dioxide upregulates the inhibited endogenous hydrogen sulfide pathway in rats with pulmonary hypertension induced by high pulmonary blood flow
Sulfur dioxide upregulates the inhibited endogenous hydrogen sulfide pathway in rats with pulmonary hypertension induced by high pulmonary blood flow
复制标题
二氧化硫上调高肺血流量所致肺动脉高压大鼠受抑制的内源性硫化氢通路
DOI：
10.1016/j.bbrc.2013.03.014
复制
发表时间：
2013-04-19
影响因子：
3.1
通讯作者：
Jin, Hongfang
中科院分区：
文献类型：
--
作者：
Luo, Liman;Liu, Die;Jin, Hongfang
肺动脉高压（PH）是许多疾病发生发展的重要病理生理过程。然而，负责PH发展的机制仍然未知。本研究的目的是探讨二氧化硫（SO2）对高肺血流量所致PH大鼠内源性硫化氢（H2S）通路的可能影响。与假手术组比较，分流组肺动脉收缩压（SPAP）明显升高，肺小动脉肌化动脉和部分肌化动脉比例沿着增加。与分流组相比，分流+ SO2组SPAP明显降低，肌化肺动脉百分比也降低。此外，肺组织中SO2浓度、AAT活性、AAT 2蛋白和mRNA表达水平均显著降低。给予SO2供体可缓解肺动脉压升高，减少肺动脉肌化。同时增加大鼠肺组织H2S生成量、胱硫醚-γ-裂解酶（CSE）蛋白表达、CSE、巯基丙酮酸转硫酶（MPST）和胱硫醚-β-合成酶（CBS）mRNA表达。结果提示，高肺血流量致PH大鼠肺组织内源性SO2/AAT 2通路和内源性H2S生成均下调。而SO2可通过上调内源性H2S途径降低肺动脉压，改善肺血管病变。(C)2013 Elsevier Inc. All rights reserved.
Pulmonary hypertension (PH) is an important pathophysiological process in the development of many diseases. However, the mechanism responsible for the development of PH remains unknown. The objective of the study was to explore the possible impact of sulfur dioxide (SO2) on the endogenous hydrogen sulfide (H2S) pathway in rats with PH induced by high pulmonary blood flow. Compared with sham group, the systolic pulmonary artery pressure (SPAP) in the shunt group was significantly increased, along with the increased percentage of muscularized arteries and partially muscularized arteries of small pulmonary arteries. Compared with the shunt group, SPAP in the shunt + SO2 group was significantly decreased, and the percentage of muscularized pulmonary arteries was also decreased. Additionally, rats that developed PH had significantly lower levels of SO2 concentration, aspartate aminotransferase (AAT) activity, protein and mRNA expressions of AAT2 in pulmonary tissues. Administration of an SO2 donor could alleviate the elevated pulmonary arterial pressure and decrease the muscularization of pulmonary arteries. At the same time, it increased the H2S production, protein expression of cystathionine-gamma-lyase (CSE), mRNA expression of CSE, mercaptopyruvate transsulphurase (MPST) and cystathionine-beta-synthase (CBS) in the pulmonary tissue of the rats. The results suggested that endogenous SO2/AAT2 pathway and the endognous H2S production were downregulated in rats with PH induced by high pulmonary blood flow. However, SO2 could reduce pulmonary arterial pressure and improve the pulmonary vascular pathological changes in association with upregulating endogenous H2S pathway. (C) 2013 Elsevier Inc. All rights reserved.