Sulfur Dioxide Inhibits Extracellular Signal-regulated Kinase Signaling to Attenuate Vascular Smooth Muscle Cell Proliferation in Angiotensin II-induced Hypertensive Mice.
Sulfur Dioxide Inhibits Extracellular Signal-regulated Kinase Signaling to Attenuate Vascular Smooth Muscle Cell Proliferation in Angiotensin II-induced Hypertensive Mice.
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二氧化硫抑制细胞外信号调节激酶信号传导，从而减弱血管紧张素 II 诱导的高血压小鼠的血管平滑肌细胞增殖。
DOI：
10.4103/0366-6999.189927
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发表时间：
2016-09-20
影响因子：
6.1
通讯作者：
Du JB
中科院分区：
文献类型：
--
作者：
Wu HJ;Huang YQ;Chen QH;Tian XY;Liu J;Tang CS;Jin HF;Du JB
阐明血管平滑肌细胞（VSMC）增殖的机制对于预防和治疗血管重构和逆转增生性病变具有重要意义。以往的研究表明，气体信号分子二氧化硫（SO2）可以抑制血管紧张素II （AngII）诱导的VSMC增殖，但SO2抑制血管紧张素II （AngII）诱导的VSMC增殖的机制尚未完全阐明。本实验旨在探讨SO2是否能抑制AngII诱导的高血压小鼠VSMC的增殖。将36只雄性C57小鼠随机分为对照组、AngII组和AngII + SO2组。AngII组和AngII + SO2组小鼠在背部皮下植入胶囊型AngII泵，缓释剂量为1000 ng·kg−1·min−1。此外，在AngII + SO2小鼠腹腔注射SO2供体。测定尾动脉动脉血压。采用弹性纤维染色法测定主动脉厚度，检测主动脉组织中增殖细胞核抗原（PCNA）和磷酸化细胞外信号调节激酶（P-ERK）水平。采用高效液相色谱-荧光法测定血清和主动脉组织匀浆上清液中SO2的浓度。在体外研究中，将A7R5细胞系的VSMC分为6组：对照、AngII、AngII + SO2、PD98059 （ERK磷酸化抑制剂）、AngII + PD98059和AngII + SO2 + PD98059。Western blotting检测PCNA、ERK、P-ERK的表达。动物实验中，与对照组相比，AngII显著升高小鼠血压（P < 0.01），使小鼠主动脉壁增厚（P < 0.05）， PCNA表达升高（P < 0.05）。SO2对AngII诱导的全身性高血压和血管壁厚度均有降低作用（P < 0.05）。抑制AngII诱导的PCNA、P- erk表达升高（P < 0.05）。细胞实验中，ERK磷酸化抑制剂PD98059阻断了SO2对VSMC增殖的抑制作用（P < 0.05）。ERK信号通路参与SO2通过ERK信号通路抑制血管内皮细胞增生的机制。
Clarifying the mechanisms underlying vascular smooth muscle cell (VSMC) proliferation is important for the prevention and treatment of vascular remodeling and the reverse of hyperplastic lesions. Previous research has shown that the gaseous signaling molecule sulfur dioxide (SO2) inhibits VSMC proliferation, but the mechanism for the inhibition of the angiotensin II (AngII)-induced VSMC proliferation by SO2 has not been fully elucidated. This study was designed to investigate if SO2 inhibited VSMC proliferation in mice with hypertension induced by AngII. Thirty-six male C57 mice were randomly divided into control, AngII, and AngII + SO2 groups. Mice in AngII group and AngII + SO2 group received a capsule-type AngII pump implanted under the skin of the back at a slow-release dose of 1000 ng·kg−1·min−1. In addition, mice in AngII + SO2 received intraperitoneal injections of SO2 donor. Arterial blood pressure of tail artery was determined. The thickness of the aorta was measured by elastic fiber staining, and proliferating cell nuclear antigen (PCNA) and phosphorylated-extracellular signal-regulated kinase (P-ERK) were detected in aortic tissues. The concentration of SO2 in serum and aortic tissue homogenate supernatant was measured using high-performance liquid chromatography with fluorescence determination. In the in vitro study, VSMC of A7R5 cell lines was divided into six groups: control, AngII, AngII + SO2, PD98059 (an inhibitor of ERK phosphorylation), AngII + PD98059, and AngII + SO2 + PD98059. Expression of PCNA, ERK, and P-ERK was determined by Western blotting. In animal experiment, compared with the control group, AngII markedly increased blood pressure (P < 0.01) and thickened the aortic wall in mice (P < 0.05) with an increase in the expression of PCNA (P < 0.05). SO2, however, reduced the systemic hypertension and the wall thickness induced by AngII (P < 0.05). It inhibited the increased expression of PCNA and P-ERK induced by AngII (P < 0.05). In cell experiment, PD98059, an ERK phosphorylation inhibitor, blocked the inhibitory effect of SO2 on VSMC proliferation (P < 0.05). ERK signaling is involved in the mechanisms by which SO2 inhibits VSMC proliferation in AngII-induced hypertensive mice via ERK signaling.
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影响因子：
5
作者：
Sun, Yan;Tian, Yue;Du, Junbao
通讯作者：
Du, Junbao
二氧化硫通过内皮依赖性和独立机制放松大鼠主动脉
影响因子：
2.1
作者：
Wang, Y. -K.;Ren, A. -J.;Lin, L.
通讯作者：
Lin, L.
影响因子：
4.5
作者：
Zhang, Quanxi;Meng, Ziqiang
通讯作者：
Meng, Ziqiang
内源性二氧化硫对野百合碱所致大鼠肺动脉高压的影响
影响因子：
8.2
作者：
Jin, Hong-fang;Du, Shu-xu;Du, Jun-bao
通讯作者：
Du, Jun-bao
影响因子：
8.3
作者：
Raij, L
通讯作者：
Raij, L