| Objective:To investigate the effects of Rosuvastatin on heart function, ventricular remodeling, myosin heavy chain (MHC), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in the rats of acute myocardial infarction.Methods:Sixty Sprague-Dawley rats were randomly divided into sham operation (no coronary ligation) rats (S group, n=10) and acute myocardial infarction (AMI) rats (n=50) received a ligation of left anterior descending coronary artery.24 hours after successful modelling,36 survived rats were randomly divided into Rosuvastatin gavage group (R group, n=18) and AMI control group (M group, n=18). The rats in Rosuvastatin administration group received a gastric gavage of Rosuvastatin at 10mg/kg/d for eight weeks. The rats in AMI control group and sham operation group were give a gastric gavage of normal saline at the same dosage. Following 8-week administration, the surviving rats in each group were examined by echocardiography, hemodynamics and blood biochemical inspection. All rats were subsequently sacrificed and their hearts were taken out to detect left ventricular weight index (LVWI), left ventricular long axis (LVLA) and cross sectional area of myocardial cells(CSA). Picric acid-Sirius red staining was used to detect type I and type III collagen volume fraction (CVF) in non-infarction zone (NIZ). The index of cardiomyocyte apoptosis in NIZ was tested by TNUEL staining. The expression of MHC, MMP-2 and TIMP-2 mRNA, as well as MMP-2 and TIMP-2 protein in NIZ, were respectively measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry staining.Result:(1) There was no significant difference of serum lipid, aspartate aminotransferase (AST), creatinine (Cr) and creatine kinase (CK) among different groups.(2) Compared with group S, the groups of M and R showed a significantly increased left ventricular end diastolic diameter (LVEDD), but a significantly decreased left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) (all P<0.05). Compared with group M, group R had a significantly decreased LVEDD, but significantly increased LVFS and LVEF(all P<0.05). (3) Compared with group S, the groups of M and R exhibited significantly decreased left ventricular systolic pressure (LVSP) and the maximum change rate of left ventricular pressure rise and fall (±dp/dtmax), but a significantly increased left ventricular end diastolic pressure (LVEDP) (all P<0.01). Compared with group M, group R showed significantly increased LVSP and±dp/dtmax, but a significantly decreased LVEDP(all P<0.01).(4) Compared with that in group S, LVWI (P<0.05), LVLA (P<0.05) and CSA (P <0.01) significantly increased in group M and group R. Compared with that in group M, the indexes of LVWI (P< 0.05), LVLA(P< 0.05) and CSA (P< 0.01) significantly decreased in group R.(5) Compared with that in group S, type I CVF, typeⅢCVF and the index of cardiomyocyte apoptosis in NIZ increased significantly in both groups of M and R(all P<0.01). Compared with that in group M, all these three indexes list above decreased significantly in group R(all P<0.01).(6) Compared with that in group S, a-MHC mRNA expression significantly decreased, butβ-MHC mRNA expression significantly increased in NIZ in both groups of M and R(all P<0.01). Compared that in group M, mRNA expression of a-MHC was significantly higher butβ-MHC was significantly lower in group R(all P<0.05).(7) Compared with that in group S, mRNA and protein expression of MMP-2 and TIMP-2 in NIZ significantly increased in both groups of M and R(all P<0.01). Compared with that in group M, mRNA and protein expression of MMP-2 and the expression ratio of MMP-2/TIMP-2 significantly decreased, but TIMP-2 expression significantly increased in group R(all P<0.05).Conclusion:Rosuvatatin effectively improves cardiac remodeling, hemodynamics and heart function following acute myocardial infarction. It is able to reverse the phenotype change of MHC, to attenuate myocardial interstitial collagen remodeling, and to reduce cardiomyocyte apoptosis in non-infarction zone of the left ventricle. However, the improvement effects of Rosuvatatin on ventricular remodeling and heart function may be independent of its lipid-lowering function, but may be associated with its down-regulation of MMP-2 and MMP-2/TIMP-2 ratios, as well as its up-regulation of TIMP-2 expression. |
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