首页|铁超载损害线粒体功能诱导中性粒细胞衰老抑制其杀菌能力加重小鼠腹膜炎

铁超载损害线粒体功能诱导中性粒细胞衰老抑制其杀菌能力加重小鼠腹膜炎

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目的 探讨铁超载对中性粒细胞功能及感染的影响及可能机制。方法 将C57BL/6小鼠随机分为对照组和铁超载组,每组10只。腹腔注射大肠杆菌,HE染色观察肝、脾组织的铁沉积,比色法检测中性粒细胞铁水平,血细胞计数板和瑞氏染色检测中性粒细胞的比例和形态,衰老相关β半乳糖苷酶(SA-β-Gal)染色评估中性粒细胞衰老情况,Western blot法检测P16蛋白表达检测中性粒细胞的衰老情况,LB涂板法检测中性粒细胞的杀菌功能,JC-1染色检测中性粒细胞线粒体膜电位、ATP试剂盒检测线粒体功能。结果 与对照组相比,铁超载组小鼠的肝及脾组织铁含量显著升高,存活时间更短;中性粒细胞数量、形态没有显著差异,但杀菌能力显著降低;P16表达升高,SA-β-Gal阳性细胞增加;线粒体膜电位降低,ATP显著减少。结论 铁超载通过抑制中性粒细胞功能,从而加重腹膜炎的发生。
Iron overload impairs mitochondrial function,induces neutrophil aging,inhibits its bactericidal ability,and exacerbates mouse peritonitis
Objective To explore the effects of iron overload on neutrophil function and peritonitis,as well as the possible mechanisms.Methods C57BL/6 mice were randomly divided into a control group and an iron overload group(10 mice in each group).Acute peritonitis model was induced by intraperitoneal injection of E.coli.The iron deposition in liver and spleen was assessed using H&E staining and the iron level in neutrophils was quantified by colorimetric analysis.The proportion and morphology of neutrophils were evaluated by blood cell counting plate and MGG staining,and the cellular aging of neutrophils was determined by senescence-associated β-galactosidase(SA-β-Gal)staining.The protein expression levels of P16 in neutrophils was detected using Western blot analysis and the bactericidal function of neutrophils was detected by LB smears.The mitochondrial membrane potential and mitochondrial function of neutrophils were detected by JC-1 staining and ATP kit,respectively.Results Compared with the control group,mice in the iron overload group exhibited following effects,including significantly higher iron content in the liver and spleen,a shorter survival time,significantly reduced bactericidal ability of neutrophil with no significant differences in the quantity or morphology,aggravated aging in neutrophils(indicated by increased expression of P16 and a higher number of SA-β-Gal positive cells),and decreased mitochondrial membrane potential and ATP levels.Conclusion Iron overload aggravates peritonitis by reducing the bactericidal ability of neutrophils.

iron overloadperitonitisneutrophilcell senescencebactericidal abilitymitochondrial function

米洋澜、韩瑞丽、吴若琳、陈黄韬、叶菁、魏晓丽

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延安大学基础医学院,陕西延安 716000

空军军医大学基础医学院病理学教研室,陕西西安 710032

西安交通大学第二附属医院神经外科,陕西西安 710004

铁超载 感染 中性粒细胞 细胞衰老 线粒体功能

国家自然科学基金

82170589

2024

细胞与分子免疫学杂志
中国免疫学会,第四军医大学

细胞与分子免疫学杂志

CSTPCD北大核心
影响因子:0.817
ISSN:1007-8738
年,卷(期):2024.40(9)