H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension
H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension
复制标题
H2S 抑制野百合碱诱导的肺动脉高压大鼠肺动脉内皮细胞炎症
DOI：
10.1038/labinvest.2016.129
复制
发表时间：
2017-03-01
影响因子：
5
通讯作者：
Jin, Hongfang
中科院分区：
文献类型：
--
作者：
Feng, Shasha;Chen, Siyao;Jin, Hongfang
本研究旨在探讨硫化氢（H2S）对野百合碱（MCT）诱导的肺动脉高压大鼠肺动脉内皮炎症的抑制作用及其可能机制。24只雄性Wistar大鼠随机分为对照组、MCT组和MCT+ H2S组。培养人肺动脉内皮细胞（HPAEC），分为对照组、MCT组、MCT+ H2S组和H2S组. MCT给药后3周，使用右心导管插入术测定肺动脉压。观察肺血管形态学改变及炎性细胞浸润情况。在体内和体外测定内源性H2S水平、胱硫醚-γ-裂解酶（CSE）表达和炎性细胞因子。Western blotting法检测NF-κB p65和IκBα的磷酸化水平，并检测NF-κB p65核转位及其DNA结合活性。MCT给药后3周发生肺动脉高压和血管重塑，肺组织炎症浸润和细胞因子水平升高，与体内和体外NF-κB通路激活相关。而MCT组内源性H2S/CSE通路表达下调。相比之下，H2S供体显著降低了MCT处理大鼠的肺动脉压、肺血管结构重塑，并增加了肺部炎症浸润和细胞因子水平。同时，H2S可逆转NF-κB通路的激活.肺动脉内皮细胞H2S/CSE通路下调参与了MCT处理的肺动脉高压大鼠的肺炎症反应。H2S通过抑制NF-κB通路减轻内皮细胞炎症反应.
This study aimed to determine whether hydrogen sulfide (H 2 S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+ H 2 S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+ H 2 S, and H 2 S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H 2 S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H 2 S/CSE pathway was downregulated in MCT rats. By contrast, an H 2 S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H 2 S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H 2 S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H 2 S attenuated endothelial inflammation by inhibiting the NF-κB pathway.