Rapamycin reverse lipopolysaccharide-induced acute lung injury through acti-vating autophagy flux
10.11665/j.issn.1000-5048.20150515
- VernacularTitle:雷帕霉素激活自噬流逆转脂多糖所致的急性肺损伤
- Author:
Hengguang ZHAO
;
Fuling LUO
- Publication Type:Journal Article
- Keywords:
lipopolysaccharide;
sepsis;
autophagy;
rapamycin;
3-methyladenine
- From:
Journal of China Pharmaceutical University
2015;(5):605-609
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to examine the effects of autophagy on the lipopolysaccharide(LPS)-induced acute lung injury (ALI)and to analyze the possible mechanism.Kunming mice of clean grade were randomly divided into 6 groups:control group(saline;ip);model group(LPS 10 mg/kg;ip);RAP group(rapamycin 6 mg/kg;ip);RAP+LPS group (RAP 6 mg/kg and LPS 10 mg/kg;ip);3-MA group (3-methyladenine 300 μg/kg;ip);and 3-MA+LPS group (3-MA 300 μg/kg and LPS 10 mg/kg;ip).6 h after LPS injection;mortality was checked.Neutrophil aggregation;and the expressions of TNF-α;LC3 and P62 in lung tissue were checked by fluo-rescence microscopy and Western blot.The results revealed a higher mortality;neutrophil infiltration and TNF-αexpression and significantly increased levels of autophagy marker LC3-II and P62 in LPS group;in RAP+LPS group;pretreatment with RAP notably reversed LPS-induced neutrophil infiltration and TNF-αexpression;LC3-II were further slightly increased;while P62 was significantly decreased;in 3-MA+LPS group;pretreatment of 3-MA slightly decreased LC3-II expression;P62;neutrophil infiltration and TNF-αremained almost the same to those in LPS group.These data suggesed that;in sepsis;autophagy flux in the lung tissue is partially blocked;and RAP help to alleviate LPS-induced lung injury;which might through promoting autophagosome maturation;smoothing autophagy flux;and eventually to mitigate pulmonary inflammation.
