Participation of autophagy in acute lung injury induced by seawater.
Seawater drowning can lead to acute lung injury (ALI). However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of autophagy in seawater-induced ALI, by which we can further understand the molecular mechanism and develop new methods for prevention and treatment of seawater-induced ALI. In this study, electron microscopy, western blot analysis, and RT-PCR were used to detect autophagy in lung tissues. Moreover, arterial blood gas analysis, lung weight coefficient, TNF-α, IL-8 in bronchoalveolar fluid (BALF), histopathology were used to detect the lung injury of seawater exposure. An inhibitor of autophagy (3-Methyladenine, 3-MA) was injected intraperitoneally before seawater exposure to further explore the role of autophagy in ALI. Electron microscopy revealed increasing autophagosomes in alveolar epithelial cell in seawater group compared with the control. The transcription and expression levels (mRNA and protein levels) of the LC3 II significantly increased in lung tissue of seawater group compared with those in control group. Furthermore, the alterations of autophage were basically consistent with the changes in arterial blood gas, lung weight coefficient, TNF-α, IL-8 in BALF and morphologic findings. In addition, inhibition of autophagy by 3-MA partly ameliorated seawater-induced ALI, as indicated by reduced lung weight coefficient and TNF-α in BALF, as well as increased PaO2. In conclusion, seawater aspiration triggered autophagy, and autophagy may be a scathing factor responsible for ALI induced by seawater.
1Third Ward of VIP, 323 Hospital of PLA, Xi'an, China.
Qiu-ping
QP
Liu
Dang-xia
DX
Zhou
Pu
P
Lin
Xiao-li
XL
Gao
Lei
L
Pan
Fa-guang
FG
Jin
D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015701:Near Drowning / Q000150:complications / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053120:Respiratory Aspiration / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012623:Seawater / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000225:Adenine; D016209:Interleukin-8; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C526109:Anxa3 protein, rat; C025946:3-methyladenine