| Objective: In recent years, with immunohistochemistry and cell biology development, it has been a gradual shift from the myocardial substantial study to myocardial interstitial tissue research. Extracellular matrix collagen content increased will result in systolic and diastolic stiffness increased, while collagen content reduction will cause the heart to expand or even rupture. Several studies have shown that myocardial fibrosis in ventricular remodeling is an important aspect, which decreases the ventricular compliance, increase the stiffness of heart, leads to myocardial ischemia, ventricular arrhythmia, and systolic and diastolic dysfunction. All of these are important risk factors for the patients with coronary heart disease developed congestive heart failure. To prevent and reverse the above changes has become an important goal of treatment. Therefore, the study of collagen and its influencing factors have gradually become a research hotspot. The current research suggests that erythropoietin (erythropoietin, EPO) can not only promote red blood cell production, but also has a strong protective effect of cells that can prevent the endothelial cells and myocardial cells apoptosis, promote angiogenesis and improve heart function. But the effect of EPO and its mechanism on collagen remodeling with myocardial ischemia-reperfusion injury or myocardial infarction is unclear.In this study, an animal model of myocardial ischemia-reperfusion was established, and EPO was applied. Myocardial infarct size and myocardial collagen remodeling were observed after myocardial ischemia-reperfusion injury, to provide a theoretical basis and new ideas for the ischemic heart disease and heart failure prevention and treatment.Methods: 54 healthy male Sprague Dawley rats were randomly divided into normal control group (Sham group), ischemia-reperfusion group (I/R group) and EPO intervention group (EPO group). Rat models of myocardial ischemia-reperfusion were induced by ligating left anterior decending coronary artery 45 minutes and reperfusion. The rats in EPO group were immediately given EPO 3000IU/kg with intraperitoneal injection, for 3 days. Respectively, after 48 hours, 14 days, 21 days of the operation, myocardial infarct size was measured by TTC staining, total collagen content in border areas was measured by Masson staining, collagenâ… mRNA and collagenâ…¢mRNA expression in border areas was measured by RT-PCR, collagenâ… protein and collagenâ…¢protein expression in border areas was measured by immunohistochemistry, and typeâ… /â…¢collagen ratio was calculated.All data were analyzed with SPSS version 17.0 statistical software. The comparison among groups was analyzed by One-Way ANOVA and S-N-K test.Results: (1)The effects on myocardial infarct size: In comparison with Sham group, rats infarct size in I/R group and EPO group was significantly increased at 48h, 14d and 21d (P <0.01).In comparison with I/R group, rats infarct size in EPO group was significantly decreased by 26.6%,26.7% and 34.8% (P<0.01) at 48h, 14d and 21d.(2)The effects of EPO on total collagen content in border areas: In comparison with Sham group, total collagen content in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01).In comparison with I/R group, total collagen content in border areas in EPO group was significantly decreased by 33.6% (P <0.01),30.1%(P<0.05) and 69.3%(P<0.01) at 48h, 14d and 21d. (3) The effects of EPO on typeâ… ,â…¢collagen protein expression in border areas: In comparison with Sham group, typeâ… collagen protein expression in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01).In comparison with I/R group, typeâ… collagen protein expression in border areas in EPO group was significantly decreased by 41.5%,42.7% and 39.7%(P<0.01) at 48h, 14d and 21d; Meanwhile, in comparison with Sham group, typeâ…¢collagen protein expression in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01). In comparison with I/R group, typeâ…¢collagen protein expression in border areas in EPO group was significantly decreased by 34.4%, 30.6% and 23.9% (P<0.01) at 48h, 14d and 21d. (4) The effects of EPO on typeâ… /â…¢collagen protein ratio in border areas: In comparison with Sham group, typeâ… /â…¢collagen protein ratio in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01).In comparison with I/R group, typeâ… /â…¢collagen protein ratio in border areas in EPO group was significantly decreased by 10.9%, 20.3% and 23.7% (P <0.01 ) at 48h, 14d and 21d. (5) The effects of EPO on typeâ… ,â…¢collagen mRNA expression in border areas: In comparison with Sham group, typeâ… collagen mRNA expression in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01).In comparison with I/R group, typeâ… collagen mRNA expression in border areas in EPO group was significantly decreased by 20.9%,17.2% and 35.7%(P<0.01) at 48h, 14d and 21d; Meanwhile, in comparison with Sham group, typeâ…¢collagen mRNA expression in border areas in I/R group and EPO group was significantly increased at 48h, 14d and 21d(P<0.01). In comparison with I/R group, typeâ…¢collagen mRNA expression in border areas in EPO group was significantly decreased by 14.6% (P <0.05), 18.5% (P <0.01) and 15.2% (P <0.01) at 48h, 14d and 21d.Conclusion:1 After acute myocardial ischemia-reperfusion injury in rats myocardial infarct size was significantly increased, the total collagen content in border areas was significantly increased, typeâ… ,â…¢collagen mRNA and proteins expression was significantly increased, and the typeâ… /â…¢collagen ratio was significantly increased.2 After EPO was applied, compared with myocardial ischemia-reperfusion group, myocardial infarct size in EPO group was significantly decreased, the total collagen content in border areas was significantly decreased, typeâ… ,â…¢collagen mRNA and proteins expression was significantly decreased, and the typeâ… /â…¢collagen ratio was significantly decreased. These results indicate that, EPO can reduce infarct size, suppress excessive proliferation of myocardial collagen, improve cardiac diastolic and systolic function, and then inhibit ventricular remodeling. |
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