Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.
Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.
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DOI：
10.1016/j.intimp.2011.01.011
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发表时间：
2011-06
影响因子：
5.6
通讯作者：
Weimin Yang;D. Qiang;Min Zhang-;Li-mei Ma;Yonghui Zhang;Chen Qing;Yun-Hua Xu;Chunlan Zhen;
中科院分区：
文献类型：
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作者：
Weimin Yang;D. Qiang;Min Zhang-;Li-mei Ma;Yonghui Zhang;Chen Qing;Yun-Hua Xu;Chunlan Zhen;
异毛喉素是从中国云南毛喉鞘蕊花（Coleus forskohlii）中分离得到的。我们假设，异福司可林预处理衰减的过程中，由脂多糖（内毒素）诱导的急性肺损伤，并在本调查进行了测试。本研究采用三种急性肺损伤模型：大鼠原位肺灌流模型、大鼠内毒素休克模型和小鼠内毒素休克模型。此外，在人单核白细胞中评价了脂多糖刺激的促炎细胞因子产生。在原位灌流的大鼠肺中，预先灌流异福司可林（100和200μM）和地塞米松（65μM，阳性对照）可抑制脂多糖（10 mg/L）诱导的肺中性粒细胞粘附率、髓过氧化物酶活性、肺重量湿/干比、通透性-表面积乘积值和肿瘤坏死因子（TNF）-α水平的增加。在大鼠中，用异福司可林（5、10和20 mg/kg，i. p.）和地塞米松（5 mg/kg，i. p.）显著降低脂多糖（6 mg/kg i. v.）引起支气管肺泡灌洗液中有核细胞、中性粒细胞计数和蛋白质含量以及血浆髓过氧化物酶活性增加。肺组织病理学显示，在异福司可林和地塞米松预处理的大鼠中，脂多糖诱导的形态学变化不太明显。在小鼠中，在给予致死剂量的脂多糖（62.5mg/kg，i. v.，40%的存活率（如果未治疗）。在人单核白细胞中，异毛喉素（50、100和200μM）和地塞米松（10μM）预孵育降低了脂多糖（2μg/mL）诱导的细胞因子TNF-α、白细胞介素（IL）-1β、IL-6和IL-8的分泌。总之，异福司可林预处理可减轻几种模型中脂多糖诱导的急性肺损伤，并参与下调脂多糖诱导的炎症反应和促炎细胞因子TNF-α、IL-1β、IL-6和IL-8。
Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates processes of acute lung injury induced by lipopolysaccharide (endotoxin) and tested it in the present investigation. Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200μM) and dexamethasone (65μM, positive control) inhibited lipopolysaccharide (10mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lethal dose lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200μM) and dexamethasone (10μM) pre-incubation lowered lipopolysaccharide (2μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of lipopolysaccharide-induced inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.