Expression and clinical value of seven different matrix metalloproteinases in anti-tuberculosis drug-induced liver injury mouse model
Objective To explore the expression and clinical value of seven different matrix metalloproteinase(MMP)in mouse model of anti-tuberculosis drug induced liver injury.Methods A total of 120 male Kunming species mice,SPF grade,6 weeks old,weight 18-24 g,were divided into six groups,with 20 mice in each group by random block methe.One group was set as the control group,after infection with Mycobacterium tuberculosis,the five groups were intragaically treated with Isoniazid(INH)45 mg/(kg·d)(INH group),Rifampicin(RIF)90 mg/(kg·d)(RIF group),Ethambutol(EB)135 mg/(kg·d)(EB group),and Pyrazinamide(PZA)180 mg/(kg·d)(PZA group)respectively.The dose of four anti-tuberculosis durg was the same as above(quadruple drug group)to establish a mouse model of anti-tuberculosis drug-induced liver injury.The expression levels of MMP-1,2,3,7,9,13,and 14 in serum of mouse models were detected by enzyme-linked immunosorbent assay at 12 h,1,2 and 3 weeks after drug administration,and their correlation with liver index changes were analyzed to explore the role of different MMP in anti-tuberculosis drug-induced liver injury.Results After 12 h of administration,compared with control group,the expression of MMP-7 in RIF group was up-regulated,with statistical significance(P<0.05).There was no significant difference in liver index of MMP-1,2,3,9,13,14 among all groups(P>0.05).Compared with the control group,the expressions of MMP-2 and MMP-7 in INH group,RIF group,and quadruple drug group were up-regulated,and the liver index was increased,with statistical significances(P<0.05).There was no significant difference in expressions of MMP-1,3,9,13,14,and liver index between groups compared with control group(P>0.05).After 2 and 3 weeks of continuous administration of the drug,compared with the control group,the expressions of MMP-2,7 and MMP-9 in serum of mice in RIF group,INH group,and quadruple drug groups were upregulated,and the liver index was increased,with statistical significances(P<0.05).There was no significant difference in the expression level of other MMP and liver index among all groups compared with the control group(P>0.05).There was no correlation between expressions of MMP-2,7,9,and liver index in INH group(P>0.05),while there was no correlation between MMP-2,7,9 and liver index in the quadruple drug group(P>0.05).There was a positive correlation between MMP-7 and liver index in RIF group(r=0.981,P<0.05).Conclusion The serum levels of MMP-2,7,and MMP-9 in mice with anti-tuberculosis drug induced liver injury are significantly elevated,indicating that the inflammatory response mediated by MMP-2,MMP-7,and MMP-9 is closely related to anti-tuberculosis drug induced liver injury.MMP-7 can be used to predict the severity of anti-tuberculosis drug induced liver injury.
Matrix metalloproteinase-2Matrix metalloproteinase-7Matrix metalloproteinase-9Anti-tuberculosis drug-induced liver injuryMouse model