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首页> 外文期刊>American Journal of Physiology >Dopamine inhibits pulmonary edema through the VEGF-VEGFR2 axis in a murine model of acute lung injury
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Dopamine inhibits pulmonary edema through the VEGF-VEGFR2 axis in a murine model of acute lung injury

机译：在急性肺损伤的小鼠模型中，多巴胺通过VEGF-VEGFR2轴抑制肺水肿

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The neurotransmitter dopamine and its dopamine receptor D2 (D2DR) agonists are known to inhibit vascular permeability factor/vascular endothelial growth factor (VEGF)-mediated angiogenesis and vascular permeability. Lung injury is a clinical syndrome associated with increased microvascular permeability. However, the effects of dopamine on pulmonary edema, a phenomenon critical to the pathophysiology of both acute and chronic lung injuries, have yet to be established. Therefore, we sought to determine the potential therapeutic effects of dopamine in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compared with sham-treated controls, pretreatment with dopamine (50 mg/kg body wt) ameliorated LPS-mediated edema formation and lowered myeloperoxidase activity, a measure of neutrophil infiltration. Moreover, dopamine significantly increased survival rates of LPS-treated mice, from 0-75%. Mechanistically, we found that dopamine acts through the VEGFVEGFR2 axis to reduce pulmonary edema, as dopamine pretreatment in LPS-treated mice resulted in decreased serum VEGF, VEGFR2 phosphorylation, and endothelial nitric oxide synthase phosphorylation. We used D2DR knockout mice to confirm that dopamine acts through D2DR to block vascular permeability in our lung injury model. As expected, a D2DR agonist failed to reduce pulmonary edema in D2DR -/- mice. Taken together, our results suggest that dopamine acts through D2DR to inhibit pulmonary edema-associated vascular permeability, which is mediated through VEGF-VEGFR2 signaling and conveys protective effects in an ALI model.
机译：已知神经递质多巴胺及其多巴胺受体D2（D2DR）激动剂可抑制血管通透性因子/血管内皮生长因子（VEGF）介导的血管生成和血管通透性。肺损伤是与微血管通透性增加相关的临床综合征。然而，多巴胺对肺水肿的影响尚未确定，肺水肿是对急性和慢性肺损伤的病理生理至关重要的现象。因此，我们试图确定在脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型中多巴胺的潜在治疗作用。与假手术对照组相比，用多巴胺（50 mg / kg体重）进行预处理可改善LPS介导的水肿形成，并降低髓过氧化物酶活性，这是嗜中性粒细胞浸润的一种指标。此外，多巴胺显着提高了LPS治疗小鼠的存活率，从0-75％。从机理上讲，我们发现多巴胺通过VEGFVEGFR2轴来减少肺水肿，因为在LPS处理的小鼠中多巴胺预处理可降低血清VEGF，VEGFR2磷酸化和内皮型一氧化氮合酶磷酸化。我们使用D2DR敲除小鼠来确认多巴胺通过D2DR来阻止我们的肺损伤模型中的血管通透性。不出所料，D2DR激动剂未能减轻D2DR-/-小鼠的肺水肿。两者合计，我们的结果表明，多巴胺通过D2DR抑制肺水肿相关的血管通透性，这是通过VEGF-VEGFR2信号传导介导的，并在ALI模型中传达保护作用。

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