Expression levels of cytokeratin 18 and matrix metalloproteinase-7 in mouse model with anti-tuberculous drug-induced liver injury
Objective To analyze the expression of cytokeratin 18(CK18)and matrix metalloproteinase-7(MMP-7)in tissues and serum of model mouse with anti-tuberculosis drug-induced liver injury(ATB-DILI),and to investigate the clinical value of CK18 and MMP-7 in the occurrence of liver injury.Methods Twenty 6-week-old SPF grade male KM mice,weighing 18-24 g,were divided into four groups according to random block method,with five mice in each group.Three groups were selected for Bacillus Calmette-Guérin(BCG)nasal drip to infect mice with Mycobacterium tuberculosis,and two groups were administrated with Isoniazid(INH)45 mg/(kg·d)and Rifampicin(RIF)90 mg/(kg·d),respectively,for three weeks,which were recorded as INH 3-week group and RIF 3-week group,and the remaining group was BCG infection control group;the untreated group was the blank control group.The BCG content of mouse lung tissue was detected by PCR,and the liver injury of mouse was observed by pathology.Liver index and lesion range were compared among all groups;the expressions of alanine aminotransferase(ALT),aspartate amin-otransferase(AST),alkaline phosphatase(ALP),γ-glutamy-ltransferase(GGT),total bilirubin(TBil),CK18,and MMP-7 in serum of all groups were compared;and the protein expressions of CK18 and MMP-7 in liver tissues of all groups were compared.Results There were no significant differences in the expressions of ALT,AST,ALP,GGT,and TBil between BCG infection control group and blank control group(P＞0.05);the expressions of ALT,AST,GGT,and TBil in INH 3-week group and RIF 3-week group were higher than those in BCG infection control group(P＜0.05).There were no significant differences in liver tissue protein expressions of CK18 and MMP-7 between blank control group and BCG infection control group(P＞0.05);the liver tissue protein expressions of CK18 and MMP-7 in INH 3-week group and RIF 3-week group were higher than those in BCG infection control group(P＜0.05).There were no significant differences in serum expressions of CK18 and MMP-7 between blank control group and BCG infection control group(P＞0.05);the serum expressions of CK18 and MMP-7 protein in INH 3-week group and RIF 3-week group were higher than those in BCG infection control group(P＜0.05).There were no significant differences in liver index and lesion range between blank control group and BCG infection control group(P＞0.05);and the liver index and lesion range of INH 3-week group and RIF 3-week group were higher than those of BCG infection control group(P＜0.05).Conclusion CK18 and MMP-7 may affect ATB-DILI.Clarifying the expression levels of CK18 and MMP-7 and intervening in advance can reduce the risk of ATB-DILI.
Mmatrixmetalloproteinase-7Cytokeratin 18Anti-tuberculosis drug-induced liver injuryMouse model
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