Celastrol attenuates ventilator induced lung injury in mouse through inhibition of MAPK pathway

Previous studies have shown that celastrol has anti-inflammatory, anti-oxidative and anti-tumor activities, but little is known about its protective effects on ventilator induced lung injury (VILI). This study is aimed to investigate the effects of celastrol on VILI and explore its potential mechanism.

A total of 40 ICR male mice aged 7-9 weeks were randomly divided into 4 groups (n=10 per group): control group (Con), control + celastrol group (Con+Ce), mechanical ventilation group (Ven) and mechanical ventilation + celastrol group (Ven+Ce). The lungs were collected for histological examination, detection of W/D, and MPO, MDA, SOD, inflammatory cytokines (IL-1β, IL-6, IL-10 and TNF-α) by ELISA, p-P₃₈ and p-JNK 1/2 protein by Western blotting, and collagen-1 and TGF-β mRNA expression by RT-PCR.

The W/D in the Ven group was significantly higher than the W/D in the Con group and the Ven+Ce group (both P<0.01). Mechanical ventilation for 4 h markedly increased lung MPO and MDA activity, TNF-α, IL-1β and IL-6, but dramatically reduced SOD and IL-10 (all P<0.01). However, celastrol pre-treatment compromised the increased MPO, MDA, TNF-α, IL-1β, IL-6 (all P<0.01) and significantly increased SOD (P=0.035<0.05) and IL-10 (P<0.01). In addition, mRNA level of collagen-1 and TGF-β as well as p-P₃₈ and p-JNK 1/2 protein expression increased significantly (P<0.01) after mechanical ventilation, which however were markedly reduced in the presence of celastrol pre-treatment.

Celastrol pre-treatment may exert anti-oxidative and anti-inflammatory effects and related lung fibrosis to attenuate VILI in mice, which may be related to the inhibition of p-P₃₈ and p-JNK 1/2 by MAPK pathway.