血流感染患者外周血铁死亡相关指标与病情严重程度的相关性

The relationship between the changes in peripheral blood ferroptosis indices and the severity of condition in the patients with bloodstream infections

目的 分析血流感染患者外周血铁代谢指标和铁死亡基因表达与疾病严重程度的相关性。方法 选取2022年8月至2023年5月安徽医科大学第二附属医院98例血流感染患者为研究对象,根据是否发生脓毒症分为非脓毒症组(n=51)和脓毒症组(n=47),另外选取体检健康人20名为对照组;脓毒症患者根据病情严重程度分为一般脓毒症组(n=18)和脓毒性休克组(n=29)。比较各组入院48 h内外周血血清铁代谢指标、铁调素及铜蓝蛋白水平;实时荧光定量逆转录PCR(RT-qPCR)法检测铁死亡相关基因[谷胱甘肽过氧化物酶4(GPX4)、血红素加氧酶-1(HO-1)、热休克蛋白B1(HSPB1)]的表达水平。结果 共纳入98例血培养阳性的单种细菌性血流感染患者,分离出病原菌共计98株,其中革兰阴性菌63株(64.29%),革兰阳性菌30株(30.61%),真菌5株(5.10%);血流感染脓毒症组患者以革兰阴性菌感染为主,与非脓毒症组比较差异有统计学意义(P<0.05)。三组铁代谢指标血清铁、铁蛋白、转铁蛋白、总铁结合力以及铁调素和铜蓝蛋白水平整体差异有统计学意义(P<0.05),铁死亡基因GPX4、HO-1和HSPB1的mRNA表达在总体上差异有统计学意义(P<0.05)。血流感染脓毒症组患者血清中铁代谢相关蛋白如铁蛋白、铁调素和铜蓝蛋白以及铁死亡相关基因HO-1和HSPB1的mRNA水平均显著高于非脓毒症组及对照组(P<0.05),而GPX4 mRNA水平则显著低于非脓毒症组及对照组(P<0.05)。同样地,脓毒性休克组患者血清中铁蛋白、铁调素、铜蓝蛋白以及HSPB1和HO-1的mRNA表达水平均显著高于一般脓毒症组(P<0.05),而GPX4 mRNA表达水平则显著低于一般脓毒症组(P<0.05)。相关性分析结果显示,血清中铁蛋白、铁调素、铜蓝蛋白水平与脓毒症严重程度呈显著正相关(P<0.05)。结论 铁代谢相关蛋白铁调素、转铁蛋白和铜蓝蛋白以及铁死亡相关基因GPX4、HO-1和HSPB1的mRNA表达水平与血流感染脓毒症的发生发展密切相关,其机制还需深入研究。

Objective To analyze the relationship of iron metabolism indices and ferroptosis genes differentially expressed in peripheral blood with disease severity in the patients with bloodstream infections.Methods A total of 98 patients with bloodstream infections in the Second Hospital of Anhui Medical University from August 2022 to May 2023 were chosen as research subjects,and were divided into two groups based on whether or not sepsis occurred:non-sepsis group(n=51) and sepsis group(n=47).Furthermore,20 healthy persons were chosen as the control group;sepsis patients were divided into general sepsis group(n=18) and sepsis shock group(n=29) according to the severity of the condition.Serum iron metabolism indices,hepcidin,and ceruloplasmin levels were compared in the three groups 48 hours after admission,and real-time quantitative polymerase chain reaction(RT-qPCR) was used to detect genes related to ferroptosis,such as glutathione peroxidase 4(GPX4),heme oxygenase-1(HO-1) and heat shock protein B1(HSPB1).Results The study comprised 98 individuals who had monospecific bacterial bloodstream infections,and a total of 98 strains of pathogenic bacteria were isolated,including 63(64.29%)gram-negative bacteria,30(30.61%) gram-positive bacteria,and 5(5.1%)fungi;patients in the sepsis group mainly had gram-negative bacterial infections,and there were significant differences between the non-sepsis group and the sepsis(P<0.05).There were significant differences in serum iron,ferritin,transferrin,total iron binding capacity,hepcidin,and ceruloplasmin levels among the three groups(P<0.05),the mRNA expression of ferroptosis genes GPX4,HO-1 and HSPB1 was significantly different in general(P<0.05).Ferritin,hepcidin,ceruloplasmin levels,and the ferroptosis-related genes HO-1 and HSPB1 mRNA levels were all significantly higher in the sepsis group than in the non-sepsis group and the control group(P<0.05),whereas GPX4 mRNA levels were significantly lower than in the non-sepsis group and the control group(P<0.05).Similarly,ferritin,hepcidin,ceruloplasmin levels,and the HO-1 and HSPB1 mRNA levels were significantly higher in the sepsis shock group compared to the general sepsis group(P<0.05),while GPX4 mRNA expression was significantly lower(P<0.05).Serum levels of ferritin,hepcidin,and ceruloplasmin were positively correlated with the severity of sepsis(P<0.05).Conclusions The expression levels of iron metabolism-related proteins hepcidin,transferrin and ceruloplasmin,and ferroptosis-related genes GPX4,HO-1 and HSPB1 mRNA are directly associated with the occurrence and development of sepsis in bloodstream infection,and the exact mechanism needs further study.