| ObjectiveObjective: With the development of modern medical technology, the mortality of Acutemyocardial infarction(AMI) is gradually decreasing, but, ventricular remodeling after Acutemyocardial infarction(AMI) caused the incidence and mortality of heart failure is obviouslyincreased. Matrix metalloproteinases(MMPs) is the key enzyme to degradation of extracellularmatrix, decide the ventricular remodeling, and matrix metalloproteinases-9(MMP-9) is a kind ofMMPs, playing a key role in ventricular remodeling after AMI. MK(Midkine, MK) is a kind ofnewly discovered heparin combining growth factor, previous research is mainly to discuss therole of MK in neoplastic disease, apoptosis process, inflammation progress, traumatic repair andso on. Recently foreign studies show MK play the protective effect in myocardial throughinhibiting apoptosis, promoting blood capillary generation. Using MK immediately after acutemyocardial infarction(AMI) if has the effect to ventricular remodeling and if it could inhibit thedegradation of extracellular matrix to protect myocardial is reported rarely at domestic andforeign. This thesis investigate the effect of midkine on ventricular remodeling and serum matrixmetalloprote- inase-9(MMP-9) expression in rats with acute myocardial infarction(AMI) bymaking acute myocardial infarction rats model, in order to discussion the function andmechanism of MK in ventricular remodeling.Methods: Sixty male Wistar rats were divided into four groups by random number samplingmethod, n=15: Control group(control group), Sham-operated group(Sham group), Acute infarctmodel group(AMI group), MK treatment group(MK group). AMI model was established vialigation of left anterior descending coronary artery, after the Model maked success, rats in MKgroup were given injected MK(1μg/10μL/rat) immediately after acute myocardial infarction.Four weeks later, the rats in each group were weighed and their hemodynamic parameters weremeasured; After Blood from the abdominal aorta, with the ELISA method for measuring serumlevels of MMP-9 expression; Then the rats were killed, whole heart and lungs was observed,whole heart weighed, then the heart body weight ratio were calculated; Crosscutting leftventricular from the ligation line perpendicular to the long axis of the heart, Paraffin-embeddedthe part of Apical, then sliced from the bottom to the apex of heart, some were performedMASSON staining, thickness and length of infracted free wall, infarct size of left ventricular,infarct area and non-infarcted myocardial collagen volume fraction(CVF) were measured, andobservated the left ventricular infarct area and non-infarcted myocardial collagen morphology, the others were done HE staining to observe myocardial cells and inflammatory cells in infarctand non-infarcted area,and the generation of capillaries in the border of infarcted area.Results: 1. Ventricular remodeling and heart dysfunction in AMI group were more sever than inControl group and Sham group (P<0.05), Ventricular remodeling and heart function in MKgroup were improved significantly compared with AMI group (P<0.05). 2. The infarcted area ofleft ventricular free wall in MK group were significantly smaller than AMI group[(24.39±0.07)vs.(40.24±0.07), P<0.05], the length of left ventricular free wall in MK group were significantly lessthan AMI group[(7.31±0.04) mm vs. (9.92±0.06) mm, P<0.05], and the thickness of leftventricular free wall in MK group were thicker than AMI group[(0.57±0.03)mm vs. (0.90±0.04)mm,P<0.05]. 3. Collagen formation of infarcted in MK group were obviously higher than AMIgroup [(80.73±0.03)vs.(62.50±0.04),P<0.05], while collagen formation of non-infarcted in MKgroup were obviously less than AMI group[(4.87±0.04)vs.(8.02±0.03),P<0.05]. 4. Capillaryformation surrounding myocardial infarction obviously in MK group were higher than AMIgroup. 5. Serum MMP-9 expression in AMI group were significantly higher than Control groupand Sham group [(6.93±0.09)ng/ml vs.(4.66±0.06)ng/ml and(4.71±0.06)ng/ml,both P<0.05],andserum MMP-9 expression in MK group were significantly less than MK group[(5.33±0.06)ng/mlvs. (6.93±0.09)ng/ml, P<0.05].Conclusion: After AMI injecting MK immediately can obviously decrease the serum MMP-9expression, inhibit the degradation of extracellular matrix, and promote collagen formation atmyocardial infarction area, increase the free wall thickness in infarction area significantly, thelength of infarcted free wall and area significantly smaller, reduce the collagen formation in noninfarctedarea, can improve significantly vasomotion function at rat heart, effectively slow earlyinfarction area the turgor exhibition, promote the own repair of infarction area, inhibit ventricularremodeling processes; MK can effectively restrain ventricular remodeling at rat after AMI,reduce serum MMP-9 expression is one way of MK playing myocardial protection; MK canpromote surrounding area capillary formation, thus obviously narrow the infarction area,delaying the ventricular remodeling processes. |
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