Experimental study of MMP-2 inhibitor treatment of experimental autoimmune myocarditis in Lewis rats / 中国应用生理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the inhibitor of matrix metalloproteinase-2 (MMP-2) (2R)-2-[5-[4-[ ethyl-methylamino] phenyl [thiophene-2-sulfonylamino]-3-methylbutyric acid (TISAM) therapeutic effect on experimental autoimmune myocarditis (EAM) in Lewis rats.</p><p><b>METHODS</b>Treatment protocol of oral administration of 5 mg/kg TISAM once a day for 14 days was performed on EAM Lewis rats. EAM Lewis rats were divided into 3 groups treatment in early, middle and later stage respectively (n = 20). After experiment at the designate time point, the rats were euthanatized and hearts were harvested. Cardiac inflammatory score, fibrosis score and content, and infiltration of macrophages and T lyminflammatory score, fibrosis score and content, and infiltration of macrophages and T lymphocytes, message RNA (mRNA) expression of matrix metalloproteinase (MMP)-2 and MMP-9 and protein activity of gelatinase were determined.</p><p><b>RESULTS</b>TISAM treatment in early phase was invalid (treatment started from the creation of the model), treatment in middle and later phase was effective (treatment started from 7 and 14 day after the creation of the model).</p><p><b>CONCLUSION</b>Inhibitor of MMP-2 can block ventricular remodeling in middle stage in EAM Lewis rats. The mechanism maybe alleviate the inflammatory cell cardiac infiltration, decrease the mRNA expression of MMP-2 at transcript level and downregulate gelatinase activity at protein level.</p>