首页> 外文期刊>American Journal of Physiology >Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation
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Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation

机译:DocosaheNoic酸通过衰减内质网应力和炎症而抑制了偏异度诱导的肺动脉高压

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Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATcl) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macro-phage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.
机译:内质网(ER)应激和炎症有助于肺动脉高压(pH)发病机制。以前,我们证实了二十二碳六烯酸(DHA)可以改善缺氧诱导的pH值。然而,关于DHA和偏菌碱(MCT)诱导的pH之间的联系很少。因此,我们的目标是评估DHA对大鼠MCT诱导的pH对MCT引起的pH的影响和分子机制。 MCT诱导大鼠pH。每天在预防组(MCT注射后)和逆转组(MCT注射后2周后2周后)治疗大鼠。在4周后,评估平均肺动脉压(MPAP),右心室(RV)肥大指数和形态学和免疫组化分析。使用大鼠肺动脉平滑肌细胞(PASMC)来研究DHA对血小板衍生生长因子(PDGF)-BB刺激的细胞增殖的影响。 DHA减少了MPAP和减毒肺血管重塑和RV肥大,其与抑制ER应力相关。 DHA阻断了PDGF-BB对PASMCs的致动作用,并通过抑制活化的T细胞-1(NFATCL)表达和活化和调节细胞周期相关蛋白的核因子阻止细胞周期。此外,DHA在肺癌中改善炎症和抗肺动脉抑制的宏观噬菌体和T淋巴细胞积累。这些发现表明DHA可以通过降低ER应激,抑制细胞增殖和炎症来保护MCT诱导的pH。

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