Chen Rui, Liu Peijing, Yan Jinchuan, Gu Yuchun
Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.
Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China. Email:
Zhonghua Jie He He Hu Xi Za Zhi. 2014 Feb;37(2):109-12.
To investigate the effects of docosahexaenoic acid (DHA) on hypoxia-induced pulmonary arterial hypertension(PAH) and the mechanism.
PAH was induced by chronic intermittent hypoxia for 21 days in vivo. Forty male Sprague-Dawley rats were randomly divided into 4 groups (n = 10, each):a normal control group, DHA-treated groups in normoxia and hypoxia, and a PAH group. At the end of study, mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy and the index of wall thickness of small pulmonary artery (WT% and WA%) among groups were compared. The changes of pulmonary arterial smooth muscle cell (PASMC) proliferation were determined by MTT in vitro. Migration assay was performed using the Boyden chamber. Real-time quantitative PCR was performed to quantify mRNA levels of the smooth muscle cell phenotype markers SM-α-actin, calponin and SM 22α under normoxic or hypoxic conditions, in the absence or presence of DHA.
DHA treatment significantly lowered mPAP [(22.7 ± 1.8) mmHg (1 mmHg = 0.133 kPa)], reduced thickening of small pulmonary artery wall [WT%:(21.6 ± 4.1)%, WA%: (52.0 ± 2.9)% ] and alleviated ventricular hypertrophy (34.2 ± 2.2) % compared to those of the hypoxic group (P < 0.05). DHA inhibited the proliferation, migration and phenotype switching of PASMCs induced by hypoxia in vitro.
DHA therapy reduced mPAP in a rat model of hypoxia-induced PAH and this effect was linked with inhibition of pulmonary vascular remodelling.
研究二十二碳六烯酸(DHA)对缺氧诱导的肺动脉高压(PAH)的影响及其机制。
在体内通过慢性间歇性缺氧21天诱导PAH。40只雄性Sprague-Dawley大鼠随机分为4组(每组n = 10):正常对照组、常氧和缺氧条件下的DHA治疗组以及PAH组。在研究结束时,比较各组的平均肺动脉压(mPAP)、右心室肥厚以及小肺动脉壁厚度指数(WT%和WA%)。体外采用MTT法测定肺动脉平滑肌细胞(PASMC)增殖的变化。使用Boyden小室进行迁移实验。在常氧或缺氧条件下,在有或无DHA存在的情况下,通过实时定量PCR定量平滑肌细胞表型标志物SM-α-肌动蛋白、钙调蛋白和SM 22α的mRNA水平。
与缺氧组相比,DHA治疗显著降低了mPAP[(22.7±1.8)mmHg(1 mmHg = 0.133 kPa)],减少了小肺动脉壁增厚[WT%:(21.6±4.1)%,WA%:(52.0±2.9)%],并减轻了心室肥厚(34.2±2.2)%(P < 0.05)。DHA在体外抑制了缺氧诱导的PASMC增殖、迁移和表型转换。
DHA治疗可降低缺氧诱导的PAH大鼠模型中的mPAP,且这种作用与抑制肺血管重塑有关。