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[二十二碳六烯酸对缺氧诱导的肺动脉高压的影响]

[Effects of docosahexaenoic acid on hypoxia-induced pulmonary arterial hypertension].

作者信息

Chen Rui, Liu Peijing, Yan Jinchuan, Gu Yuchun

机构信息

Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.

Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China. Email:

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2014 Feb;37(2):109-12.

Abstract

OBJECTIVE

To investigate the effects of docosahexaenoic acid (DHA) on hypoxia-induced pulmonary arterial hypertension(PAH) and the mechanism.

METHODS

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.

RESULTS

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.

CONCLUSION

DHA therapy reduced mPAP in a rat model of hypoxia-induced PAH and this effect was linked with inhibition of pulmonary vascular remodelling.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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