Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models
Yang, Weimin1; Qiang, Dongjin1; Zhang, Min1; Ma, Limei1; Zhang, Yonghui1; Qing, Chen1; Xu, Yunlong2; Zhen, Chunlan1; Liu, Jikai2; Chen, Yan-Hua3
通讯作者Yang, WM (reprint author), Kunming Med Coll, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650031, Peoples R China
2011-06-01
发表期刊INTERNATIONAL IMMUNOPHARMACOLOGY
ISSN1567-5769
卷号11期号:6页码:683-692
摘要Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isuforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). 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 200 mu M) and dexarrethasone (65 mu M, positive control) inhibited lipopolysaccharide (10 mg/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)-alpha levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5 mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/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, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5 mg/kg, iv., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 mu M) and dexamethasone (10 mu M) pre-incubation lowered lipopolysaccharide (2 mu g/mL) induced secretion of the cytokine TNF-alpha, and interleukins (IL)-1 beta, 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 inflammatory responses and proinflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-8. (C) 2011 Elsevier B.V. All rights reserved.
关键词Acute Lung Injury Isoforskolin Lipopolysaccharide Inflammation Cytokine
学科领域Immunology ; Pharmacology & Pharmacy
DOI10.1016/j.intimp.2011.01.011
收录类别SCI
语种英语
WOS记录号WOS:000291505900007
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/5353
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Kunming Med Coll, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650031, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China
3.E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27834 USA
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Yang, Weimin,Qiang, Dongjin,Zhang, Min,et al. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2011,11(6):683-692.
APA Yang, Weimin.,Qiang, Dongjin.,Zhang, Min.,Ma, Limei.,Zhang, Yonghui.,...&Chen, Yan-Hua.(2011).Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.INTERNATIONAL IMMUNOPHARMACOLOGY,11(6),683-692.
MLA Yang, Weimin,et al."Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models".INTERNATIONAL IMMUNOPHARMACOLOGY 11.6(2011):683-692.
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