重组人脑利钠肽通过抑制大鼠JAK/STAT信号通路改善创伤性急性肺损伤。
Recombinant human brain natriuretic peptide ameliorates trauma-induced acute lung injury via inhibiting JAK/STAT signaling pathway in rats.
作者信息
Song Zhi, Zhao Xiu, Gao Yan, Liu Martin, Hou Mingxiao, Jin Hongxu, Cui Yan
机构信息
From the Department of Emergency and Critical Care Medicine (Z.S., Y.G., M.H., H.J., Y.C.), The General Hospital of Shenyang Military District; and Department of Oral Medicine (X.Z.), Shenyang Medical College, Shenyang, Liaoning Province, China; and Department of Internal Medicine (M.L.), University of Nebraska Medical Center, Omaha, Nebraska.
出版信息
J Trauma Acute Care Surg. 2015 May;78(5):980-7. doi: 10.1097/TA.0000000000000602.
BACKGROUND
JAK/STAT signal pathway plays an important role in the inflammation process of acute lung injury (ALI). This study aimed to investigate the correlation between recombinant human brain natriuretic peptide (rhBNP) and the JAK/STAT signaling pathway and to explore the protective mechanism of rhBNP against trauma-induced ALI.
METHODS
The arterial partial pressure in oxygen, lung wet-dry weight ratios, protein content in bronchoalveolar lavage fluid, the histopathologic of the lung, as well as the protein expressions of STAT1, JAK2, and STAT3 were detected.
RESULTS
Sprague-Dawley rats were randomly divided into five groups: a control group, a sham-operated group, an ALI group, an ALI + rhBNP group, and an ALI + AG490 group. At 4 hours, 12 hours, 1 day, 3 days, and 7 days after injury, injured lung specimens were harvested. rhBNP pretreatment significantly ameliorated hypoxemia and histopathologic changes and alleviated pulmonary edema in trauma-induced ALI rats. rhBNP pretreatment reduced the phosphorylated protein and total protein level of STAT1. Similarly to JAK-specific inhibitor AG490, rhBNP was shown to significantly inhibit the phosphorylation of JAK2 and STAT3 in rats with trauma-induced ALI.
CONCLUSION
Our experimental findings indicated that rhBNP can protect rats against trauma-induced ALI and that its underlying mechanism may be related to the inhibition of JAK/STAT signaling pathway activation.
背景
JAK/STAT信号通路在急性肺损伤（ALI）的炎症过程中起重要作用。本研究旨在探讨重组人脑利钠肽（rhBNP）与JAK/STAT信号通路之间的相关性，并探索rhBNP对创伤性ALI的保护机制。
方法
检测动脉血氧分压、肺湿重与干重比值、支气管肺泡灌洗液中的蛋白质含量、肺组织病理学以及STAT1、JAK2和STAT3的蛋白表达。
结果
将Sprague-Dawley大鼠随机分为五组：对照组、假手术组、ALI组、ALI + rhBNP组和ALI + AG490组。在损伤后4小时、12小时、1天、3天和7天，采集损伤的肺标本。rhBNP预处理显著改善了创伤性ALI大鼠的低氧血症和组织病理学变化，并减轻了肺水肿。rhBNP预处理降低了STAT1的磷酸化蛋白和总蛋白水平。与JAK特异性抑制剂AG490相似，rhBNP在创伤性ALI大鼠中显著抑制JAK2和STAT3的磷酸化。
结论
我们的实验结果表明，rhBNP可以保护大鼠免受创伤性ALI的影响，其潜在机制可能与抑制JAK/STAT信号通路激活有关。
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