| AIM:To investigate the effect and the mechanism of atrophic factor Muscle Ring Finger-1 (MuRF-1) on heart function and cardiac troponin I (cTnI) in myocardial infarction rats and the correlations between MuRF-1 and cTnI.METHODS:Rats either with coronary artery ligation or with sham operation (48 rats) were divided into 4 groups:Sham (sham-operated) group, MI (myocardial infarction) group, MG-132 (N-[(Phenylmethoxy)carbonyl]-L-leucyl-N-[(1 S)-1-formyl-3-methyl butyl]-L-leucinamide) group and TNF-a (tumor necrosis factor-alpha) group. Animals were treated with proteasome inhibitor MG-132, TNF-αor received saline with intraperitoneally injections. Hemodynamics, N-terminal pro b-type natriuretic peptide (NT-proBNP) and pathology were measured. Both mRNA relative expression and protein relative expression of MuRF-1 and cTnI were checked either by Real-time PCR and in situ hybridization or by western blot in left ventricular, then analysis the correlation between MuRF-1 and cTnI.RESULTS:Compared with MI group and TNF-a group, the mortality and the morbidity had the decreased tendency in MG-132 group, and NT-proBNP level as well as the left ventricular end-diastolic pressure (LVEDP) were significantly decreased (P<0.05 and P<0.01, respectively), left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (+dp/dtmax) were pronounced increased (P<0.01), also the heart injury was amended after MG-132 treatment. Compared with Sham group, the mRNA and protein relative expressions of MuRF-1 were predominantly increased in MI group (P<0.05), and the cTnl levels were decreased (P<0.05). MG-132 could depress MuRF-1 (P<0.05) level as well as enhance cTnI (P<0.01) level both in mRNA and protein expression. In contrast, TNF-a challenged rats had shown the worsen heart failure, further reduced cTnI level and raised MuRF-1 level. Our data also showed that the mRNA and protein expression of MuRF-1 had significant negitive correlation with the expression of cTnI in all groups.CONCLUSION:These data suggested that atrophic factor MuRF-1 is significantly increased in heart on chronic heart failure rats. And it will aggravate heart disfunction by depressing cTnI level. Inhibition proteasome activity could down-regulate MuRF-1 expression in rat heart on chronic heart failure model. MuRF-1 may play an important role in chronic heart failure. |
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