Mechanism of protective effect of sulforaphane against radiation-induced lung injury in mice / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the radioprotective function and its mechanism of Sulforaphane (SF) in mice acute radiation-induced lung injury.Methods Totally 40 female C57BL/6J mice were equally divided into 5 groups randomly.Group A,treated by SF 3 mg/kg plus radiation;group B,treated by SF 5 mg/kg plus radiation;group C,treated by SF 10 mg/kg plus radiation;radiation group with a single dose of 12 Gy in 6 MV X-ray by a linear accelerator,and control group with sham radiation.The mice in drug group were administered intraperitoneally with different concentration of SF every other day from 7 d before irradiation to 7 d after irradiation,while the same volume of DMSO plus physiological saline solvent was given in the control and radiation groups.After being sacrificed at 14 d of SF administration,the pathomorphological changes of mice were observed in trauma lung tissue,the positioning and expression of NLRP3 was observed by immunohistochemical staining,the levels of IL-6,TNF-α and TGF-β1 in bronchoalveolar lavage fluid (BALF) were measured by ELISA,the expressions of NLRP3 and IL-1β mRNA in lung tissue were assayed by qRT-PCR,the expressions of NF-κB p65,NLRP3 and IL-1β proteins in lung tissue were assayed by Western blot,the activity of NF-κB was detected by EMSA.Results In comparison with radiation group,there was an obvious amelioration in pathological injury of lung tissue in the treatment groupsthe expression of NLRP3 in lung tissue decreased;the concentration of NLRP3 in the drug intervention group (SF 10 mg / kg) markedly decreased (F =42.750,P ＜ 0.05).the IL-6,TNF-a and TGF-β1 levels in BALF decreased (tIL-6 =-62.65-21.00;tTNF-α =-32.18-16.57;tTGF-β1 =-58.22-46.11,P ＜ 0.05);the expressions of NLRP3 and IL-1β mRNA markedly decreased (tNLRP3 =-6.56-5.68;tIL-1β =-29.75--21.20,P ＜ 0.05),and the expressions of NF-κB p65,NLRP3 and IL-1β proteins decreased (tNF-κB p65 =-34.00--1.71,tNLRP3 =-25.01--16.91,tIL-1β =-73.70--55.14,P ＜ 0.05);the relative expressions of NF-κB p65 and NLRP3 were reduced in a dose-dependent manner (r =0.945,0.926);and the activity of NF-κB were obviously reduced (tNF-κB =-38.68,-614.82,-2 831.40,P ＜ 0.05).Conclusions Sulforaphane effectively alleviates the RILI in lung of mice by downregulating the expressions of inflammatory factor NLRP3.