MiR·223 protects mice from acute radiation-induced lung injury by inhibiting NLRP3 / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the radioprotective function and its mechanism of miR-223 in acute radiation-induced lung injury in mice.Methods Forty female C57BL/6 J mice were randomly divided into healthy control group,irradiation group,irradiation plus miR-223 group and irradiation plus NC group.Radiation groups were exposed with a single dose of 15 Gy of 6 MV X-rays delivered by a linear accelerator.The mice in drug group were administered by tail vein injection with miR-223 agomir or agomirNC every other day from 1 d before irradiation to 14 d after irradiation.The lung tissue samples of mice were taken at 14 d post-irradiation.The pathological changes were observed by HE staining.The localization and expressions of IL-1β and IL-18 were observed by immunohistochemistry (IHC).Real-time PCR was used to detect miR-223,but NLRP3 mRNA expression in lung tissue.Western blot was used to detect the protein expressions of NLRP3 and Caspase-1,and ELISA assay was used to detect the expressions of IL-1β and IL-18 in lung homogenate.Results Radiation decreased the expression of miR-223,but increased the expression of NLRP3 in lung tissue.Administration of miR-223 agomir inhibited the expression of NLRP3 and attenuated lung inflammation.HE and IHC staining showed that miR-223 reduced the acute inflammatory response and the expressions of IL-1β and IL-18 in lung tissue compared with irradiation group (t=10.16,6.00,P＜0.05).The expressions of NLRP3 and Caspase-1 protein in lung tissue of irradiated plus miR-223 group was lower than that in the irradiation alone group (t =12.47,4.95,P＜ 0.05).ELISA assay also showed a decrease of inflammatory factors IL-1β and IL-18 in lung tissue homogenate of the irradiation plus miR-223 group (t =8.22,8.47,P＜0.05).Conclusions MiR-223 effectively reduces the secretion of radiation-induced inflammatory factors IL-1β and IL-18 by inhibiting the expression of NLRP3 in lung tissue of mice,and thus has protective effect on radiation-induced lung injury.