Abstract:
:Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague-Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood-air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results:In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood-air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood-air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Wang T,Liu C,Pan LH,Liu Z,Li CL,Lin JY,He Y,Xiao JY,Wu S,Qin Y,Li Z,Lin Fdoi
10.3389/fphar.2020.569251subject
Has Abstractpub_date
2020-12-11 00:00:00pages
569251issn
1663-9812pii
569251journal_volume
11pub_type
杂志文章abstract::The efficacy of lamotrigine in the treatment of focal epilepsies have already been reported in several case reports and open studies, which is thought to act by inhibiting glutamate release through voltage-sensitive sodium channels blockade and neuronal membrane stabilization. However, recent findings have also illust...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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abstract::Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for I...
journal_title:Frontiers in pharmacology
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abstract::The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of ...
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01212
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abstract::Wenxin Keli (WXKL) is a widely used Chinese botanical drug for the treatment of arrhythmia, which is consisted of four herbs and amber. In the present study, we analyzed the chemical composition of WXKL using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to tentatively identify 71 comp...
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abstract::Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramam...
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pub_type: 杂志文章
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abstract::Osteosarcoma (OS) is a malignant primary bone tumor with high metastatic rate. C-X-C motif chemokine ligand 6 (CXCL6) and its receptor C-X-C motif chemokine receptor 1/2 (CXCR1/2) have been found to participate in the process of carcinogenesis. In this study, we evaluated the role of CXCL6/CXCR1/2 axis in proliferatio...
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pub_type: 杂志文章
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abstract:Background:As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial antitumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored. Methods:We used cell proliferation assay, scratch and transwell experiments, and cell cycle ...
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pub_type: 杂志文章
doi:10.3389/fphar.2020.01211
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2016.00463
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00470
更新日期:2017-07-17 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2019.00256
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
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