Effects Of Heart-protecting Musk Pill On Myocardial Interstitium Reconstruction In Rabbits With Heart Failure After Myocardial Infraction

Objective: In the current study, we investigated the effects of Heart-protecting Musk Pill (HMP) by observing the pathological and hemodynamic changes and the mRNA expression levels of matrix metalloproteinase-2 (MMP-2),metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rabbits with heart failure after myocardial infraction, not only to explain the molecule mechanism of extracellular matrix remodeling of heart failure mediated by HMP, but also to clarify the new knowledge of extracellular matrix remodeling and provide a novel method for its therapeutics.Method: We established the chroinc heart failure (CHF) modles after myocardial infarct (MI) in New Zealand rabbits by ligation of the left anterior descending coronary artery. Sham group was given the same procedure but without ligation. Rabbits with CHF were divided into CHF 4W group, CHF 8W group, ENA (Enalapril) 4W group, ENA 8W group, HMP 4W group and HMP 8W group two weeks after coronary artery ligation. After 4 or 8 weeks, we evaluated hemodynamic state with PiCCO, then killed them to measure left ventricular mass index (LVMI). The pathological and morphologic changes were observed under hematoxylin-eosin staining. Collagen volume fractions (CVF) were measured using Van Gieson (VG) in non-infarct regions. The ultrastructural organizations were observed by electron microscope. The mRNA expression levels of MMP-2, MMP-9 and TIMP-1 were detected by reverse transcription PCR method.Results: (1) Comparison of hemodynamic parameters in rabbits. The cardiac output (CO), cardiac index (CI) and global ejection fraction (GEF) all increased (P<0.05) in HMP groups compared with the CHF groups. While global end diastolic volume index (GEDI) decreased in HMP groups (P<0.05). (2) LVMI comparison. LVMI values of HMP4W group and HMP8W group were smaller than that of the corresponding CHF group (P<0.05). When same action time was considered, the ENA groups and the HMP groups showed no significant statistical difference in LVMI (P>0.05). (3) Myocardial pathological changes and collagen volume fraction comparison: The HMP treatment significantly reduced inflammatory reaction; cardiac cell morphology and structure were recovered and fibroplasias inhibited to some extent, with HMP8W group showing the most visible improved effects. Myocardial CVFs were significantly reduced in HMP groups than in CHF groups. Pathological changes in ultrastructure myocardial cells and collagen fibres in HMP groups both reduced, with HMP8W group showing the most significant improvement. (4) Expression levels of MMP-2, MMP-9, TIMP-1 mRNA showed similar changes in HMP group and the corresponding ENA group, all lower than those in CHF groups. The MMP-2 mRNA expression level in HMP4W group decreased more significantly compared with HMP8W group. The mRNA expression levels of other two indicators decreased more significantly in HMP8W group than in HMP4W group.The MMP-9/TIMP-1 mRNA ratio was kept aroud 1 in HMP groups and ENA groups.Conclusion:Heart-protecting Musk Pill can improve hemodynamic disorder in rabbits with heart failure after myocardial infraction, reduc the pathological damages of myocardial cells, inhibit collagen proliferation, lower expression levels of myocardial MMP-2, and maintain dynamic balance of expression levels of MMP-9, TIMP-1 mRNA, MMP-9/TIMP-1 mRNA ratioes. As the action time persisted, the effects of improvement were more significant. This may be one of HMP's mechanisms to improve myocardial interstitium reconstruction after myocardial infraction heart failure.