【作者】 刘慧英；

【导师】 左维泽；

【作者基本信息】 石河子大学 ， 临床医学（专业学位）， 2023， 硕士

【摘要】 目的:探讨外周血CD3~+T淋巴细胞、CD4~+T淋巴细胞、CD8~+T淋巴细胞、CD4~+/CD8~+、B淋巴细胞、NK细胞、Th17细胞、Treg细胞、Th17/Treg、CD4~+IFN-γ~+T淋巴细胞、CD4~+TNF-α~+T淋巴细胞、CD8~+TFN-γ~+T淋巴细胞、CD8~+TNF-α~+T淋巴细胞等免疫细胞、细胞间比值及IFN-γ、TNF-α、IL-10细胞因子与抗结核药物性肝损伤(Anti-tuberculosis drug induced liver injury,ATDILI)的相关性,为阐明ATDILI发生的确切机制提供参考。方法:纳入石河子大学第一附属医院2021年1月至2022年1月在石河子大学第一附属医院住院及门诊部诊断为初治肺结核的患者。将2个月内发生抗结核药物性肝损伤(ATDILI)患者为观察组,将完成整个2个月强化期未发生肝损伤的肺结核患者为对照组。共收入观察组23例,对照组22例。采用我院His系统收集纳入患者治疗前一般资料及生化指标数据,收集对照组抗结核治疗2个月后、ATDILI组发生肝损伤的生化指标数据。用流式细胞术方法及ELISA法检测所有患者治疗前、观察组发生药物性肝损伤时、对照组抗结核治疗2个月后的外周血免疫细胞水平及血清细胞因子水平。运用SPSS26.0统计学软件,采用t检验、卡方检验等统计学方法进行分析,以P<0.05为差异有统计学意义。结果:(1)抗结核治疗前,观察组与对照组基本资料及生化学指标(包括性别、年龄、身高、体重、体重指数(BMI)、ALT、AST、GGT、ALP、Tbil、白细胞计数、中性粒细胞计数、淋巴细胞计数)差异无统计学差异(P>0.05)。(2)抗结核治疗前,观察组与对照组相比,外周血%CD3~+T淋巴细胞,%CD4~+T淋巴细胞、%CD8+T淋巴细胞、CD4~+/CD8~+、%B淋巴细胞、%NK细胞、%Th17细胞、%Treg细胞、Th17/Treg、%CD4~+IFN-γ~+T淋巴细胞、%CD4~+TNF-α~+T淋巴细胞、%CD8~+IFN-γ~+T淋巴细胞、%CD8~+TNF-α~+T淋巴细胞、IFN-γ、TNF-α及IL-10细胞因子差异无统计学意义(P>0.05)。(3)抗结核治疗后,观察组患者与对照组相比,%CD8~+T淋巴细胞、CD4~+/CD8~+、%NK淋巴细胞、%Th17淋巴细胞、%Treg淋巴细胞、%CD8~+IFN-γ~+T细胞、%CD8~+TNF-α~+T细胞、IFN-γ、TNF-α及IL-10细胞因子水平均与对照组有显著差异,差异有统计学意义(P<0.05)。(4)而抗结核治疗后,观察组患者与对照组相比,%CD3~+T淋巴细胞,%CD4~+T淋巴细胞、%B淋巴细胞、%CD4~+IFN-γ~+T淋巴细胞及%CD4~+TNF-α~+T淋巴细胞差异无统计学意义(P>0.05)。结论:抗结核治疗后,发生ATDILI的患者的CD8~+T、NK、TH17、Treg、CD8~+IFN-γ~+T、CD8~+TNF-α~+T细胞频率及IFN-γ、TNF-α、IL-10细胞因子水平高于未发生ATDILI的患者,并且ATDILI组患者细胞间比值出现失衡,提示上述淋巴细胞、细胞因子及细胞间的比值失衡可能参与了ATDILI的发生发展过程。更多还原

【Abstract】 Objective:To analyze the relationship between the ratio of CD3~+T cells,CD4~+T cells,CD8~+T cells,CD4~+/CD8~+,B lymphocytes,NK cells,Th17 cells,Treg cells,CD4~+IFN-γ~+T,CD4~+TNF-α~+T,CD8~+IFN-γ~+T,CD8~+TNF-α~+T and intercellular ratio and IFN-γ,TNF-α,IL-10 cytokines in the process of anti-tuberculosis drug induced liver injury(ATDILI),so as to provide a basis for the elucidation of the precise mechanisms by which ATDILI.Methods:Patients diagnosed with newly diagnosed pulmonary tuberculosis in the inpatient and outpatient departments of the First Affiliated Hospital of Shihezi University Medical College from January 2021 to January 2022 were included.The patients with anti-tuberculosis drug-induced liver injury(ATDILI)within2 months were selected as the observation group,and the patients with pulmonary tuberculosis who completed the whole 2-month intensive anti-tuberculosis process without liver injury were selected as the control group.There were 23 cases in observation group and 22 cases in control group.His system in our hospital was used to collect the general data and biochemical index data before treatment.The biochemical data of liver injury in ATDILI group were collected after 2 months of anti-tuberlosis treatment in control group.The peripheral blood immune cell levels of all patients were tested before treatment,during drug-induced liver injury in the observation group,and 2 months after anti-tuberculosis treatment in the control group were measured by flow cytometry and ELISA.Using SPSS26.0 statistical software,using t test,chi-square test statistical methods for analysis,P<0.05 was considered statistically significant.Results:(1)Before anti-tuberculosis treatment,there was no statistical difference in the basic data and biochemical indicators(including gender,age,height,weight,body mass index(BMI),ALT,AST,GGT,ALP,Tbil,white blood cell count,neutrophil count,lymphocyte count)between the observation and control groups(P>0.05).(2)There was no significant difference between observation group and control group before anti-tuberculosis treatment in peripheral blood%CD3~+T lymphocytes,%CD4~+T lymphocytes,%CD8~+T lymphocytes,CD4~+/CD8~+,%B lymphocytes,%NK cells,%Th17 cells,%Treg cells,Th17/Treg,%CD4~+IFN-γ~+T lymphocytes,%CD4~+TNF-α~+T lymphocytes,CD8~+IFN-γ~+T lymphocytes,%CD8~+TNF-α~+T lymphocytes,IFN-γ,TNF-α,IL-10 cytokine(P>0.05).(3)After anti-tuberculosis treatment,in the observation group,compared with the control group,%CD8~+T lymphocytes,CD4~+/CD8~+ratio,%NK lymphocyte frequency,%Th17 lymphocytes,%Treg lymphocytes,%CD8~+IFN-γ~+T cells,%CD8~+TNF-α~+T cells,IFN-γ,TNF-α,IL-10 cytokine levels were significantly higher than the control group,the difference was statistically significant(P<0.05).(4)After anti-tuberculosis treatment,there was no significant difference in%CD3~+T lymphocytes,%CD4~+T lymphocytes,%B cells,%CD4~+IFN-γ~+T lymphocytes,%CD4~+TNF-α~+T cells between the patients in the observation group and the control group(P>0.05).Conclusion:The level of CD8~+T,NK cells,Th17 cells,Treg cells,CD8~+IFN-γ~+T cells,CD8~+TNF-α~+T cells and IFN-γ,TNF-α,IL-10 cytokines in patients with ATDILI were higher than those in patients without ATDILI after anti-tuberculosis treatment,indicating perhaps that the imbalance of lymphocytes,cytokines and cell ratio was involved in the occurrence and development of ATDILI.更多还原