免疫功能和SAA、MMP-9、MMP-14在抗结核药物性肝损伤中的临床评估

Clinical Evaluation of Immune Function and SAA,MMP-9 and MMP-14 in Liver Injury Caused by Anti-Tuberculous Drugs

目的探讨抗结核药物性肝损伤患者免疫功能变化,及血清淀粉蛋白酶A(serum amylase A,SAA)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、基质金属蛋白酶14(matrix metalloproteinase 14,MMP-14)在抗结核药物性肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)中的临床价值和应用意义。方法选取2019年7月至2020年7月昆明市第三人民医院收治的抗结核药物性肝损伤患者115例,根据肝损伤不同类型,将患者分为A、B、C、D 4个亚组,选取同期健康体检者35例设为对照组(E组)。比较免疫功能和SAA、MMP-9、MMP-14在不同亚组的变化及表达水平,以及与ATB-DILI严重程度分级之间的关系。结果A组患者CD4+T淋巴细胞计数低于E组,两两比较,差异具有统计学意义(P<0.05);SAA与MMP-9的表达量高于其他3组,组间差异有统计学意义(P<0.05);C组患者MMP-14的表达量高于其他3组,差异具有统计学意义(P<0.05)。SAA和MMP-9与ATB-DILI严重程度分级具有相关关系(r=0.687,P<0.05;r=0.811,P<0.05)。结论CD4+T淋巴细胞在部分ATB-DILI患者中有所降低,提示该类患者存在免疫功能低下,免疫屏障受损可能与肝损伤有一定相关性。SAA、MMP-9和MMP-14在不同肝损伤类型患者中均有程度不一的升高,ATBDILI严重程度与SAA和MMP-9的表达量密切相关,SAA和MMP-9、MMP-14有望成为临床ATB-DILI严重程度的评估指标。

Objective To explore the changes of immune function in patients with anti-tuberculous druginduced liver injury(ATB-DILI),and to explore the clinical value and application significance of serum amylase A(SAA),matrix metalloproteinase 9(MMP-9)and matrix metalloproteinase 14(MMP-14)in anti-tuberculosis drug liver injury.Methods A total of 115 patients with anti-tuberculosis drug-induced liver injury admitted to the Third People’s Hospital of Kunming from July 2019 to July 2020 were selected.Based on types of liver injury,the patients were divided into 4 subgroups A,B,C and D,and 35 healthy subjects underwent health check during the same period were selected as control group(group E).The changes and expression levels of immune function,SAA,MMP-9 and MMP-14 in different subgroups were compared,as well as their relationship with ATB-DILI severity grade.Results The CD4+count of group A patients was lower than that of group E,and the difference was statistically significant(P<0.05).The expression levels of SAA and MMP-9 in gronp A were higher than the other three groups,and the difference between the groups was statistically significant(P<0.05).The expression of MMP-14 in group C was higher than that of the other three groups,and the difference was statistically significant(P<0.05).SAA and MMP-9 were correlated with the severity of anti-tuberculosis drug liver injury(r=0.687,P<0.05;r=0.811,P<0.05).Conclusion CD4+counts were reduced in some patients with ATB-DILI,suggesting that these patients have low immune function,and the impaired immune function may be related to liver injury.SAA,MMP-9 and MMP-14 increased in different degrees in patients with different types of anti-tuberculosis drug liver injury.The severity of liver injury is closely related to the expression of SAA and MMP-9.SAA,MMP-9 and MMP-14 are expected to be the evaluation indicators of the severity of clinical ATB-DILI.