摘要
目的探讨脓毒症患者早期外周血T淋巴细胞亚群(CD3^+、CD4^+、CD8^+)和自然杀伤细胞(natural killer cells,NK细胞)水平与患者肠道损伤和预后的相关性,为临床治疗脓毒症提供免疫治疗依据。方法采用前瞻性的病例对照研究方法,以2018年9月至2019年5月宁夏医科大学总医院重症医学科(ICU)收治的61例脓毒症患者为研究对象(脓毒症组),选择同期17例普通术后非脓毒症患者作为对照(非脓毒症组)。收集所有研究对象入住ICU 24 h内外周静脉血样本,测定T淋巴细胞亚群和NK细胞水平。同时,从脓毒症组中选择既往无慢性胃肠道和慢性肾功能不全的患者35例,测定其和非脓毒症组患者血清肠型脂肪酸结合蛋白(intestinal fatty acid binding protein,I-FABP)、D-乳酸水平。记录所有研究对象的年龄、性别、基础疾病。评估脓毒症组入ICU 24 h内急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ评分),随访患者28 d生存情况。对脓毒症组和非脓毒症组之间T淋巴细胞亚群和NK细胞、I-FABP、D-乳酸水平进行比较,对比存活组和死亡组之间T淋巴细胞亚群和NK细胞水平,采用Spearman相关法分析脓毒症早期血清I-FABP、D-乳酸分别与CD3^+、CD4^+、CD8^+、NK细胞水平的相关性,采用二分类变量多因素Logistic回归分析脓毒症患者死亡的危险因素。结果与非脓毒症组相比,脓毒症组血清I-FABP、D-乳酸水平均升高[I-FABP(μg/L):18.36(14.75,28.34)vs 16.17(12.12,18.40),D-乳酸(mg/L):18.70(10.10,40.60)vs 8.85(7.10,15.76),均P<0.05],脓毒症组外周血CD3^+、CD4^+、NK细胞水平均下降[CD3^+(%):54.30(37.48,61.65)vs 60.75(48.88,69.95),CD4^+(%):24.60(17.65,32.15)vs 31.90(24.95,37.10),NK细胞(%):18.20(11.95,31.10)vs 24.70(19.30,32.65),均P<0.05],但是早期外周血CD8^+水平在两组间差异无统计学意义(P>0.05)。存活组与死亡组之间外周血CD3^+、CD4^+、CD8^+、NK细胞水平差异均无统计学意义(均P>0.05)。T淋巴细胞亚群、NK细胞和肠道损伤标志物的相关性分析显示,I-FABP与CD3^+、CD8^+呈负相关(r值分别为-0.478、-0.415,均P<0.05),但与CD4^+、NK细胞之间无相关性(均P>0.05)。D-乳酸与CD3^+、CD4^+呈负相关(r值分别为-0.344、-0.423,均P<0.05),与NK细胞呈正相关(r=0.393,P<0.05),但是D-乳酸与CD8^+之间无相关性(P>0.05)。61例脓毒症患者28 d死亡危险因素的多因素Logistic回归分析显示,仅APACHEⅡ评分是患者28 d死亡的独立危险因素[OR=1.222,95%CI:1.084~1.378,P<0.01],早期CD3^+、CD4^+、CD8^+、NK细胞水平与脓毒症患者28 d预后无关(P>0.05)。结论脓毒症早期可发生免疫抑制,其与肠道损伤相关,但是与患者预后无关。
Objective To explore the correlation between the levels of peripheral blood T lymphocyte subsets(CD3^+,CD4^+,CD8^+)and natural killer cells(NK cells)in the early stage of sepsis and intestinal injury and prognosis of patients,so as to provide the basis of immunotherapy for clinical treatment of sepsis.Methods A prospective case-control study was conducted.Sixty-one patients with sepsis admitted to Department of Critical Care Unit(ICU)of Ningxia Medical University from September 2018 to May 2019 were selected as subjects(sepsis group).Seventeen patients with common postoperative non-sepsis were used as controls(non-sepsis group).Venous blood samples were collected from all subjects within 24 h of ICU admission,and the levels of T lymphocyte subsets and NK cells were measured.At the same time,35 sepsis patients without chronic gastrointestinal tract and chronic renal insufficiency were selected from the sepsis group,and their serum levels of intestinal fatty acid binding protein(I-FABP)and D-lactic acid were measured.Age,sex,and underlying disease were recorded for all subjects.The acute physiology and chronic health evaluationⅡ(APACHEⅡscore)within 24 h of ICU in the sepsis group were evaluated,and the patients were followed up for 28 days.T lymphocyte subsets and NK cells,I-FABP,D-lactic acid levels were compared between the sepsis group and non-sepsis group.T lymphocyte subsets and NK cell levels were compared between the survival and death groups.Spearman correlation method was used to analyze the correlation between serum I-FABP and D-lactic acid in the early stage of sepsis and levels of CD3^+,CD4^+,CD8^+and NK cells,and multivariate logistic regression analysis was used to assess the risk factors of death in sepsis patients.Results Compared with the non-sepsis group,serum I-FABP and D-lactic acid levels were increased in the sepsis group[I-FABP(μg/L):18.36(14.75,28.34)vs 16.17(12.12,18.40),D-Lactic acid(mg/L):18.70(10.10,40.60)vs 8.85(7.10,15.76),all P<0.05].Peripheral blood CD3^+,CD4^+,NK cells in the sepsis group were decreased[CD3^+(%):54.30(37.48,61.65)vs 60.75(48.88,69.95),CD4^+(%):24.60(17.65,32.15)vs 31.90(24.95,37.10),NK cells(%):18.20(11.95,31.10)vs 24.70(19.30,32.65),P<0.05],but there was no significant difference in peripheral blood CD8^+levels between the two groups(P>0.05).There were no significant differences in CD3^+,CD4^+,CD8^+and NK cell levels between the survival group and death group(all P>0.05).Correlation analysis of T lymphocyte subsets,NK cells and intestinal injury markers(n=35)showed that I-FABP was negatively correlated with CD3^+and CD8^+(r=-0.478 and r=-0.415,respectively,both P<0.05),but not correlated with CD4^+and NK cells(both P>0.05).D-lactic acid was negatively correlated with CD3^+and CD4^+(r=-0.344 and r=-0.423,respectively,P<0.05),and positively correlated with NK cells(r=0.393,P<0.05),but there was no correlation between D-lactic acid and CD8^+(both P>0.05).Multivariate logistic regression analysis showed that only the APACHEⅡscore was an independent risk factor for 28-day mortality in patients with sepsis(OR=1.222,95%CI:1.084-1.378,P<0.01),but the early CD3^+,CD4^+,CD8^+,NK cell levels were not associated with 28-day prognosis in patients with sepsis(P>0.05).Conclusions Immunosuppression can occur in the early stage of sepsis,which is related to intestinal damage,but is not associated with patient prognosis.
作者
张小彬
刘丹
闫晶
雷萌萌
杨晓军
Zhang Xiaobin;Liu Dan;Yan Jing;Lei Mengmeng;Yang Xiaojun(School of Clinical Medicine,Ningxia Medical University,Yinchuan 750004,China;Department of Critical Care Medicine,General Hospital of Ningxia Medical University,Yinchuan 750004,China)
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2020年第5期682-687,共6页
Chinese Journal of Emergency Medicine
基金
"十三五"国家重点研发计划项目(2016YFD0400605)。
