Lactoferrin improves hepatic pyroptosis in mice after irradiation

作     者：Ru Zhang Jia Gu Yulu Wei Yaxing Guo Liqiang Qin Jiaying Xu Ru Zhang;Jia Gu;Yulu Wei;Yaxing Guo;Liqiang Qin;Jiaying Xu

作者机构：Department of Nutrition and Food HygieneSchool of Public HealthSoochow UniversitySuzhou 215123China Suzhou National High-tech District Center for Disease Prevention and ControlSuzhou 215011China State Key Laboratory of Radiation Medicine and ProtectionCollaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSchool of Radiation Medicine and ProtectionSoochow UniversitySuzhou 215123China 

出 版 物：《Radiation Medicine and Protection》 (放射医学与防护（英文）)

年 卷 期：2022年第3卷第1期

页      面：16-21页

学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床] 

基　　金：The study was supported by the National Natural Science Foundation of China(82073482). 

主　　题：Lactoferrin Irradiation Liver Pyroptosis Absent in melanoma 2(AIM2) 

摘      要：Objective:To investigate the effects of lactoferrin(Lf)on hepatic pyroptosis(an inflammatory form of programmed cell death)in mice exposed to radiation.Methods:A total of thirty-six BALB/c male mice were randomly divided into four groups,namely the control group,5 Gy group,5 Gyþ2 mg Lf group,and 5 Gyþ4 mg Lf group.The mice were administered whole-body ionizing radiation using a PRIMUS accelerator,with a single dose of 5 Gy and an absorbed dose rate of 2.0 Gy/min at a source-skin distance of 100 cm.Lf solution was intraperitoneally injected into the mice 2 h before and per day after radiation.The mice were sacrificed 1,3,and 9 d after radiation,and their livers were used for histopathologic examination,immunohistochemistry analysis,and Western blot analysis for absent in melanoma 2(AIM2)inflammasome pathway.Results:Histopathologic examination showed the disorder of the hepatocellular structure and the accumulation of inflammatory cells after radiation.Lf intervention inhibited hepatocellular proliferation and decreased the infiltration of inflammatory cells.Immunohistochemistry analysis indicated that AIM2 overexpression was significantly attenuated by 4 mg of Lf(t=3.065,P0.05)3 d after radiation and by 2 mg and 4 mg of Lf(t=4.032,t=2.786,P0.05)9 d after radiation.Western blot analysis showed that Lf downregulated the hepatic overexpression of AIM2,apoptosis-associated speck-like protein containing a caspase activation and recruitment domain(ASC),IL-1β,and IL-18.2 mg of Lf significantly downregulated the abovementioned protein expression 3 d(t=7.934,4.092,5.193,2.916,P0.05)and 9 d after radiation(t=5.016,3.882,9.528,P0.05 for AIM2,ASC,IL-1β).Conclusions:Lf intervention suppressed the hepatic pyroptosis in mice exposed to ionizing radiation by downregulating the protein expression of AIM2 inflammasome.