Protective effect of GW3965 on PQ-induced acute lung injury in mice via inhibition of p38MAPK signal pathway / 中华急诊医学杂志

ABSTRACT

Objective To investigate the protective effects and the possible mechanisms of GW3965, a liver X receptors (LXRs) agonist, in mice with PQ-induced acute lung injury. Methods A total of 40 male c57BL/6J mice were randomly(random number) divided into four groups. In control group, mice were intra-peritoneally injected with 0.1 mL normal saline solution twice at an interval of 10 min. In paraquat poisoning group, mice were intra-peritoneally injected with paraquat in a dose of 28 mg/kg and 0.1 mL normal saline solution 10 min later. In low dose GW3965 treatment group, mice were intra-peritoneally injected with GW3965 in a dose of 10 mg/kg 10 min after PQ administration. In high dose GW3965 treatment group, mice were intra-peritoneally injected with GW3965 in a dose of 50 mg/kg at 10 min after PQ administration. The mice were sacrifi ced at 72 h after PQ administration to collect lung tissues and blood specimens. Malonaldehyde(MDA) levels in blood were measured by thiobarbituric acid (TBA) method, and IL-1β and TNF-α levels in blood and lung tissues were measured using ELISA assay. Lung tissues were collected to determine the wet-to-dry (W/D) ratios ,histopathology changes by HE staining , and the levels of p38 MAPK, Bax and Bcl-2 were detected by Western blot as well as cell apoptosis by TUNEL. Multiple groups were compared with One-way ANOVA and pairwise comparison among groups were made by least signifi cance difference (LSD) determination. Results Compared with the control group, the PQ group had more severe lung injury, greater wet/dry weight ratio, higher MDA level in blood, higher IL-1β and TNF-α level in blood and lung tissues, higher expression of p38 MAPK, greater Bax/Bcl-2 ratio and greater numbers of cell apoptosis in lung tissues(P<0.05). GW3965 treatment attenuated all these changes(P<0.05), and the effect of GW3965 in high dose treatment group was more remarkable(P<0.05). Conclusion GW3965 significantly attenuates PQ-induced acute lung injury in mice. This effect may be associated with the inhibition of p38 MAPK signal pathway.