摘要
目的探究乳铁蛋白(lactoferrin,Lf)对放射性肠损伤的防护作用及其机制。方法小鼠随机分为对照组、10 Gy组及Lf+10 Gy组。于照射前7 d,Lf+10 Gy组给予250 mg/kg Lf灌胃,每天1次。10 Gy组和Lf+10 Gy组小鼠接受10 Gy的腹部照射。照射后3.5 d处死小鼠,收集样本测定相关指标。结果照射引起放射性肠损伤,Lf干预缓解了体重下降、肝脏氧化应激,改善了小肠病理损伤,增加反映小肠细胞增殖再生能力的Lgr5和Ki67阳性细胞数。照射引起小肠组织的铁死亡。在铁代谢途径中,Lf干预显著下调小肠二价金属转运蛋白(divalentmetal-iontransporter-1,DMT1)的表达及Fe^(2+)含量;在谷胱甘肽(glutathione,GSH)/谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)-脂质过氧化途径中,Lf干预显著上调小肠溶质载体家族7成员(solute carrier family 7 member,SLC7A11)和GPX4蛋白表达,下调酰基辅酶A合成酶长链4(acyl-CoA synthase long chain 4,ACSL4)蛋白表达并降低丙二醛(malondialdehyde,MDA)水平。结论Lf改善了放射性肠损伤,其作用机制可能与通过铁代谢与GSH/GPX4-脂质过氧化途径调节铁死亡有关。
Objective To explore the protective effect and mechanism of lactoferrin(Lf)on a radiation-induced intestinal injury.Methods Mice were randomly divided into the control group,10 Gy group,and Lf+10 Gy group.On 7 d before irradiation,the Lf+10 Gy group was given 250 mg/kg Lf by gavage daily.Mice in the 10 Gy group and Lf+10 Gy group received 10 Gy abdominal irradiation.The mice were sacrificed 3.5 d after irradiation,and the samples were collected to determine the related indexes.Results Irradiation-induced intestinal injury.Lf intervention restored weight loss,hepatic oxidative stress,and pathological intestinal damage in mice.Lf significantly increased the number of Lgr5 and Ki67 positive cells,reflecting the proliferation and regeneration ability of small intestinal cells.Irradiation-induced ferroptosis in small intestinal tissue.Via the iron metabolism pathway,Lf intervention significantly downregulated the expression of intestinal divalent metal transporter(DMT1)and Fe^(2+)content;via the GSH/GPX4-lipid peroxidation pathway,Lf intervention significantly upregulated the intestinal solute carrier family 7 members(SLC7A11)and glutathione peroxidase 4(GPX4)protein expression,downregulated acyl-CoA synthase long chain 4(ACSL4)protein expression,and reduced malondialdehyde(MDA)levels.Conclusions Lf ameliorated radiation-induced intestinal injury,possibly due to the regulation of ferroptosis through iron metabolism and the GSH/GPX4-lipid peroxidation pathway.
作者
郭雅馨
徐加英
卫蔚
李德明
秦立强
GUO Yaxin;XU Jiaying;WEI Wei;LI Deming;QIN Liqiang(Department of Nutrition and Food Hygiene,School of Public Health,Soochow University,Suzhou 215123,China;State Key Laboratory of Radiation Medicine and Radiation Protection,Soochow University,Suzhou 215123,China)
出处
《中华疾病控制杂志》
CAS
CSCD
北大核心
2023年第4期465-470,共6页
Chinese Journal of Disease Control & Prevention
基金
国家自然科学基金(82073482,82173502)
关键词
乳铁蛋白
放射性肠损伤
铁死亡
Lactoferrin
Radiation-induced intestinal injury
Ferroptosis
作者简介
通信作者:秦立强,E-mail:qinliqiang@suda.edu.cn
