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Erschienen in: Inflammation 2/2019

15.01.2019 | ORIGINAL ARTICLE

Autophagy Activation Improves Lung Injury and Inflammation in Sepsis

verfasst von: Hongying Zhao, Hongguang Chen, Meng Xiaoyin, Guotao Yang, Ying Hu, Keliang Xie, Yonghao Yu

Erschienen in: Inflammation | Ausgabe 2/2019

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Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) undergoes the process of pathological event including lung tissue dysfunction, pulmonary edema, and inflammation in sepsis. Autophagy is a cytoprotective process recognized as one of the major pathways for degradation and recycling of cellular constituents. Autophagy as a protective or maladaptive response was still confused in ALI during sepsis. Acute lung injury was performed by cecal ligation and puncture (CLP). Autophagic inducer rapacymin and inhibitor 3-MA and autophagosomal-lysosome fusion inhibitor bafilomucin (Baf) A1 and chloroquine (CQ) were administrated by intraperitoneal injection at 1 h after CLP operation. Microtubule-associated protein light chain 3 II (LC3II), Beclin 1, Rab7, and lysosome-associated membrane protein type 2 (LAMP2) were detected by western blotting. Seven-day survival rate of septic mice was observed. Histologic scores, lung wet-to-dry (W/D) weight ratio, oxygenation index (PaO2/FiO2), total cells and polymorphonuclear neutrophils (PMN) in bronchial alveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity and cytokine tumor necrosis factor (TNF)-α, high-mobility group box (HMGB)1, interleukin (IL)-6, IL-10, and monocyte chemotactic protein (MCP)1 were measured after sham or ALI operation. ALI induced the increasing expression of autophagy-related protein LC3II, Beclin 1, Rab7, and LAMP2 in CLP operation. Autophagic inducer rapacymin significantly induced the expression of LC3II, Beclin 1, LAMP2, and Rab7 in mice model of CLP, and inhibitor 3-MA reduced expression of LC3II, Beclin 1, LAMP2, and Rab7 expressions in CLP + RAP mice compared to CLP group. Compared with ALI group, Baf and CQ obviously elevated the level of LC3II and Beclin 1, and reduced the LAMP2 and Rab7 expressions in CLP + Baf group and ALI + CQ group. Compared with CLP group, autophagic inducer rapacymin improved the survival rate, histologic scores, lung wet/dry weight ratio, PaO2/FiO2, total cells, and PMNS in BALF and MPO activity and cytokines TNF-α, HMGB1, IL-6, IL-10, and MCP1 in CLP + RAP group, but there were exacerbated above indicators in CLP + 3-MA group, CLP + Baf group, and CLP + CQ group. Autophagy activation participated in the pathophysiologic process of sepsis, and alleviated the cytokine excessive release and lung injury in sepsis.
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Metadaten
Titel
Autophagy Activation Improves Lung Injury and Inflammation in Sepsis
verfasst von
Hongying Zhao
Hongguang Chen
Meng Xiaoyin
Guotao Yang
Ying Hu
Keliang Xie
Yonghao Yu
Publikationsdatum
15.01.2019
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 2/2019
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-00952-5

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