肝硬化患者的免疫功能障碍与血清壳多糖酶3样蛋白1表达的关系

The Relationship between Immune Dysfunction in Patients with Liver Cirrhosis and the Expression of Serum Chitinase-3 like Protein 1

目的:探究肝硬化患者的免疫功能障碍与血清壳多糖酶3样蛋白1(CHI3L1)表达关系。方法:招募2018年2月至2020年8月在我院就诊的160例肝硬化患者。通过Child-Pugh评分对肝病的严重程度进行分组,轻度组(n=73)和重度组(n=87)。在本院健康检查中心招募60例年龄相仿且无任何明显疾病或感染的人员作为对照组。并检测CHI3L1蛋白表达、CHI3L1浓度、MR浓度、CD3^(+)T、CD25^(+)T和CD69^(+)T水平以及血浆细胞因子的浓度。结果:对照组较轻度和重度组AST、ALT浓度升高,且轻度组较重度组升高(P<0.05)。Cr血清浓度各组比较无差异(P>0.05)。轻度组中93.15%患者为Child-Pugh A,重度组中全部为Child-Pugh B/A。重度组较轻度组肝硬化程度严重(P<0.05)。重度组和轻度组较对照组CHI3L1蛋白表达升高,重度组较轻度组升高(P<0.05)。重度组和轻度组血清CHI3L1水平较对照组升高(P<0.05),重度组较轻度组升高(P<0.05)。重度组和轻度组血清CD163和甘露糖受体(MR)水平较对照组升高(P<0.05),重度组较轻度组升高(P<0.05)。重度组和轻度组血清CD3^(+)T、CD25^(+)T和CD69^(+)T水平较对照组升高,重度组血清较轻度组升高(P<0.05)。重度组和轻度组白细胞介素(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)和干扰素(IFN-γ)浓度较对照组升高,重度组较轻度组升高(P<0.05)。Logistic回归分析,提示患者血清CHI3L1、MR、CD3^(+)T、CD25^(+)T、CD69^(+)T与患者肝硬化程度相关(P<0.05)。结论:肝硬化患者中血清CHI3L1与肝硬化严重程度呈正相关,CHI3L1促进T细胞活化、增殖和炎性细胞因子的分泌,这导致加重了免疫介导的肝损伤和纤维化的发展。

Objective:To explore the relationship between immune dysfunction and serum chitinase-3 like protein 1 expression in patients with liver cirrhosis.Methods:A total of 160 patients with cirrhosis admitted to our hospital from February 2018 to August 2020were recruited.The severity of liver disease was divided into the mild group(n=73)and the severe group(n=87)by child-Pugh score.Sixty cases of similar age without any obvious disease or infection were recruited as the control group in the health examination center of our hospital.CHI3L1 protein expression,CHI3L1 concentration,MR concentration,CD3^(+)T,CD25^(+)T and CD69^(+)T levels,and plasma cytokine concentration were detected.Results:The concentrations of AST and ALT in the control group were higher than those in the mild and severe groups,and those in the mild group were higher than those in the severe group(P<0.05).There was no difference in Cr serum concentration among the groups(P>0.05).93.15%of patients in the mild group were Child-Pugh A,and all patients in the severe group were Child-Pugh B/A.The severity of liver cirrhosis in the severe group was more severe than that in the mild group(P<0.05).The protein expression of CHI3L1 in the severe group and the mild group was higher than that in the control group,and the protein expression of CHI3L1 in the severe group was higher than that of the mild group(P<0.05).The level of serum CHI3L1 in the mild group and the mild group was higher than that in the control group(P<0.05),and the serum CHI3L1 level in the severe group was higher than that in the mild group(P<0.05).The levels of serum CD163 and MR in the severe group and the mild group were higher than those in the control group(P<0.05),and the serum CD163 and MR levels in the severe group were higher than those in the mild group(P<0.05).The levels of serum CD3^(+)T,CD25^(+)T,and CD69^(+)T in the severe and mild groups were higher than those in the control group(P<0.05),and the levels of serum CD3^(+)T,CD25^(+)T and CD69^(+)T in the severe group were higher than those in the mild group.High(P<0.05).The concentrations of interleukin(IL-1β),IL-6,tumor necrosis factorα(TNF-α)and IFN-γ in the severe and mild groups were higher than those in the control group,and those in the severe group were higher than those in the mild group(P<0.05).Logistic regression analysis showed that serum CHI3L1,MR,CD3^(+)T,CD25^(+)T,CD69^(+)T were correlated with the degree of cirrhosis(P<0.05).Conclusion:Serum CHI3L1 was positively correlated with the severity of cirrhosis in patients with cirrhosis,and CHI3L1 promoted T cell activation,proliferation and secretion of inflammatory cytokines,which aggravated the development of immune-mediated liver injury and fibrosis.