重组中期因子对大鼠心肌梗死后心室重塑及Ⅲ型前胶原氨基端肽的影响

The impact of recombinant human midkine to ventricular remodeling and PⅢNP after myocardial infarction in rats

目的研究早期应用中期因子（MDK）对大鼠心肌梗死后心室重塑的作用及对Ⅲ型前胶原氨基端肽（PⅢNP）与心功能的影响。方法结扎Wistar大鼠左冠状动脉前降支建立心肌梗死动物模型。32只大鼠随机分为3组：对照组（Sham，8只）、心肌梗死组（MI，12只）和心肌梗死＋人重组中期因子干预组（MI＋MDK，12只）。造模成功后1μg／200g人重组中期因子在梗死周围分5点注射给药。4周后，所有大鼠行血流动力学、PⅢNP、微血管、胶原的测定及心脏标本的病理学分析。结果与MI组比较，MI＋MDK组的SBP、MAP、LVSP和±dp／dtmax显著增高，而LVEDP显著降低（P〈0．01）；血清PⅢNP值显著增加（P〈0．01）。病理标本分析：与MI组相比，MI＋MDK组梗死区中胶原容积分数显著增加，非梗死区中显著减少；MI＋MDK组有更多新生血管出现（P〈0．05）；MI＋MDK组炎细胞浸润、梗死面积、心肌肥大程度、心室重量明显减轻（P〈0．01）。结论急性心肌梗死大鼠早期应用MDK能发挥血管形成和胶原刺激的作用，对延缓急性心肌梗死后心室重塑发挥重要的作用。

Objective To investigate the effect of ventricular remodeling and PIU NP after using recombinant human midkine （MDK） in early myocardial infarction in rats. Methods Acute myocardial infarction model was made by ligating the anterior descending coronary artery. Thirty two rats were randomly divided into three groups： sham operation group（Sham, n=8）, acute myocardial infarction group（MI, n= 12） and treated group （MI＋ MDK, n=12）. In MI＋MDK group, each rat was immediately treated by injecting doses of 1 μg/200 g recombinant human MDK into the border zone myocardium at five sites after the ligation succeed. After 4 weeks, all rats were detected there hemodynamics, serum P Ⅲ NP, vascular density, collagen volume and pathological analysis of cardiac specimens. Results Compared with the MI group and MI＋MDK group： systolic blood pressure （SBP）, mean aortic pressure （MAP）, left ventricular systolic pressure （LVSP） and maximum rise and decline rate of left ventricular pressure （±dp/dtmax） of MI＋MDK group were significantly increased left ventricular end diastolic pressure （LVEDP） decreased （P〈0.01）. Serum pill NP values in MI＋MDK group were increased significantly （P〈0.01）. Pathology specimens analysis： Compared with the MI group, collagen volume fraction in MI＋MDK group was increased significantly in infarct area, while in non-infarct area was reduced significantly （P〈0.01）, inflammatory cell infiltration, infarct size, myocardial hypertrophy, ventricular weight in MI＋MDK group were significantly reduced （P〈0.01）. Conclusion This study shows that in rat with acute myocardial infarction, the early application of MDK may play angiogenesis and collagen stimulating role. And it can play an important role in delaying ventricular remodeling after acute myocardial infarction.