Protective Effects of 3-Methyladenine against Lipopolysaccharide-induced Acute Lung Injury in Mice and the Mechanism Study / 中国药房

ABSTRACT

OBJECTIVE:To study the protective effects of autophagy inhibitor 3-Methyladenine (3-MA) against lipopolysac-charide(LPS)-induced acute lung injury in mice and its mechanism. METHODS:Mice were randomly divided into normal control group,model group (LPS 15 mg/kg),drug control group (3-MA 20 mg/kg),low-dose and high-dose groups (LPS 15 mg/kg+3-MA 20,40 mg/kg),with 10 mice in each group. Except for normal control group and drug control group,other groups were giv-en LPS intraperitoneally to induce acute lung injury model,and drug control group and low-dose and high-dose groups were given equivalent dose of 3-MA intraperitoneally 1 h before modeling. 6 h after modeling,lung wet/drug mass ratio (W/D) was deter-mined respectively,and pathology change of lung tissue was observed by HE staining. TNF-α,NF-κB p65,LC3BⅡ/Ⅰ and Cleaved-caspase-3 protein expression were detected by Western blot. RESULTS:Compared with normal control group,W/D, TNF-α,NF-κB p65,LC3BⅡ/Ⅰ and Cleaved-caspase-3 protein expression increased in model group (P<0.01). Compared with model group,W/D,the expression of TNF-α,NF-κB p65,LC3BⅡ/Ⅰ and Cleaved-caspase-3 protein decreased in low-dose group (P<0.05),white just only LC3BⅡ/Ⅰ protein decreased high-dose group(P<0.01). CONCLUSIONS:In LPS-induced acute lung injury model in mice,the excessive autophagy could activate the NF-κB pathway and involve the inflammatory responses and induce lung cells apoptosis. The moderate autophagy inhibition by 3-MA can ameliorate inflammatory response and protect lung tissue.