To study the protective effect of melatonin on PM2.5-induced inflammation and lymphangiogenesis in the lung of ApoE^-/- mice.

Twenty-eight male ApoE^-/- mice were randomized into: control group, PM2.5 group, melatonin group and PM2.5+melatonin group. All mice were fed with western diet for 24 weeks. From the 25th week, mice in the melatonin group and PM2.5+melatonin group were daily orally gavage with melatonin (20 mg/kg·bw) for 8 weeks; mice in the PM2.5 group and PM2.5+melatonin group were exposed to PM2.5 by tracheal instillation (5mg/kg); and mice in the control group and melatonin group were instilled with saline at the same time. After 24 h of PM2.5 exposure, mice were euthanized and weight gain and lung weight/body weight ratio in four groups were analyzed. The concentrations of inflammatory cytokines (TNF-α and IL-6) in the lung tissue of mice were measured. Immunofluorescence staining of lung tissue was visualized the lymphatic marker LYVE1 expression. Western Blot was used to assess the protein expression levels of lymphangiogenesis markers PROX1 and LYVE1, lymphangiogenesis regulatory proteins VEGF-C and VEGFR-3 in lung tissues.

The levels of TNF-α and IL-6 and the protein expressions of PROX1, LYVE1, VEGF-C and VEGFR-3in lung tissues of PM2.5 group were significantly higher than the control group (P<0.05). Moreover, the levels of TNF-α, IL-6 and the protein expressions of PROX1, LYVE1, VEGF-C and VEGFR-3 in lung tissues of the PM2.5+melatonin group were significantly lower than the PM2.5 group (P<0.05).

Ambient PM2.5 exposure obviously increases lung inflammation of ApoE^-/- mice, and may increase lymphangiogenesis in lung through regulating the VEGF-C/VEGFR-3 signaling pathway in the lung tissues; melatonin markedly improves PM2.5-induced lung inflammation and reduces lymphangiogenesis in lung.