摘要
目的:单核巨噬细胞系统参与先天性及适应性免疫应答,并具有极强的可塑性,对于肝损伤中的炎症反应、促进组织修复方面起着重要作用。本研究旨在探讨药物性肝损伤(drug-induced liver injury,DILI)患者外周血单核细胞百分比升高与疾病严重程度的相关性,并进一步检测外周血中单核细胞M1、M2亚型的水平。方法:收集170例DILI患者(分为轻中度组49例,重度及以上组121例)和100例健康体检人群(对照组)的临床资料。对3组研究对象的临床资料进行组间比较,对DILI患者单核细胞百分比、淋巴细胞百分比及淋巴细胞百分比与单核细胞百分比比值(ratio of lymphocytes to monocytes,LMR)与肝功能临床参数行相关性分析。同时收集10例健康人和13例DILI患者入院时(治疗前)及治疗2周后的清晨空腹肘静脉血,采用流式细胞术检测外周血单核细胞表面CD86(M1型单核细胞)、CD163(M2型单核细胞)的表达。结果:DILI患者单核细胞百分比与总胆红素(total bilirubin,TBil)水平呈正相关(r=0.512,P<0.01);LMR、淋巴细胞百分比与TBil水平均呈负相关(r=−0.499、r=−0.259,均P<0.01);流式细胞术结果显示:与对照组比较,DILI组患者外周血M1型单核细胞显著增加(P<0.001),M2型单核细胞减少(P=0.036),M2/M1比值显著降低(P=0.011);DILI组患者治疗前后,随着肝功能好转,M1、M2型单核细胞变化趋势发生逆转,M2/M1比值升高(P=0.034)。结论:DILI患者外周血单核细胞百分比升高、LMR降低与肝损伤严重程度有关。此外,在肝损伤进展阶段以M1型单核细胞增加为主,随着肝功能的改善,M2型单核细胞逐渐恢复。因此,靶向调控单核/巨噬细胞M1、M2极化可能作为未来治疗DILI的新策略。
Objective:The mononuclear phagocyte system participates in both innate and adaptive immune responses and exhibits remarkable plasticity,playing important roles in inflammatory response and tissue repair in liver injury.This study aims to investigate the correlation between the elevation of peripheral blood monocyte percentage in patients with drug-induced liver injury(DILI)and the severity of the disease,as well as to detect the levels of peripheral blood M1 and M2 subtypes.Methods:Clinical data were collected from 170 patients with DILI[divided into a mild to moderate group(n=49)and a severe and above group(n=121)],and 100 healthy individuals(a control group).Clinical parameters among the 3 groups were compared.Correlation analyses were conducted between the monocyte percentage,lymphocyte percentage,ratio of lymphocyte to monocyte(LMR),and clinical parameters of liver function in DILI patients.Additionally,fasting elbow venous blood samples were collected from 10 healthy individuals and 13 DILI patients upon admission(before treatment)and after 2 weeks of treatment.Flow cytometry was employed to detect the expression of CD86(M1 monocytes)and CD163(M2 monocytes)on the surface of peripheral blood monocytes.Result:The percentage of monocytes in DILI patients was positively correlated with the level of total bilirubin(TBil)(r=0.512,P<0.01).LMR and lymphocyte percentage were negatively correlated with TBil levels(r=−0.499,r=−0.259,both P<0.01).Flow cytometry results demonstrated a significant increase in M1 monocytes(P<0.001)and a decrease in M2 monocytes(P=0.036),leading to a decrease M2/M1 ratio(P=0.011)in peripheral blood of the DILI group compared to the control group.In the DILI patients,with the improvement of liver function,the trend of changes in M1 and M2 monocytes reversed,leading to an increase in the M2/M1 ratio(P=0.034).Conclusion:The increase of peripheral blood monocytes percentage and the decrease in LMR are closely associated with the severity of liver injury in DILI patients.Furthermore,during the progression of liver injury,the increase in M1 monocytes predominates,while with the improvement of liver function,M2 monocytes gradually recover.Therefore,targeting the polarization of monocytes/macrophages towards M1 or M2 phenotypes may serve as a novel therapeutic strategy for DILI in the future.
作者
周妮
王源媛
郭思琪
麦平
ZHOU Ni;WANG Yuanyuan;GUO Siqi;MAI Ping(School of Medicine,Jiangsu University,Zhenjiang Jiangsu 212013;Department of Gastroenterology,Gansu Provincial Hospital,Lanzhou 730030;First Clinical Medical School,Gansu University of Chinese Medicine,Lanzhou 730030,China)
出处
《临床与病理杂志》
CAS
2023年第12期2117-2124,共8页
Journal of Clinical and Pathological Research
