Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats
Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats
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DOI：
10.1152/ajplung.00412.2005
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发表时间：
2007-08-01
影响因子：
4.9
通讯作者：
Nagaya, Noritoshi
中科院分区：
文献类型：
--
作者：
Itoh, Takefumi;Obata, Hiroaki;Nagaya, Noritoshi
肾上腺髓质素（AM）是一种内源性多肽，对心血管系统具有多种保护作用。然而，AM对急性肺损伤的影响尚不清楚。因此，我们研究了AM输注是否改善脂多糖（LPS）诱导的大鼠急性肺损伤。大鼠随机接受AM（0.1 μ g.）kg（-1）（.）min（-1））或溶媒。动物气管内注射LPS（1 mg/kg）或盐水。在气管内滴注后6和18 h，我们进行了组织学检查和支气管肺泡灌洗，并评估肺湿/干重比作为急性肺损伤的指标。检测支气管肺泡灌洗液（BALF）中总细胞数、中性粒细胞数、肿瘤坏死因子（TNF）-α和苦参碱诱导的中性粒细胞趋化因子（CINC）水平。此外，我们评估了BALF总蛋白和白蛋白水平作为肺通透性的指标。LPS灌注引起严重的急性肺损伤，如组织学结果和肺湿/干重比所示。然而，AM输注减弱了这些LPS诱导的异常。AM可降低BALF中细胞总数、中性粒细胞数及TNF-α和CINC水平。AM还降低BALF总蛋白和白蛋白水平。此外，AM显着抑制肺泡壁细胞的凋亡所示的切割caspase-3染色。结论：持续输注AM可减轻LPS诱导的大鼠急性肺损伤。AM对急性肺损伤的这种有益作用可能通过抑制炎症、高通透性和肺泡壁细胞凋亡来介导。
Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 mu g (.) kg(-1) (.) min(-1)) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.