中期因子对大鼠心肌梗死后心室重塑的保护作用

目的观察中期因子（MK）对大鼠急性心肌梗死（AMI）后心室重塑的影响。方法成年雄性Wistar大鼠48只，随机分为4组：空白对照组（Control组）、伪手术组（sham组）、梗死模型组（AMI组）和MK干预组（MK组）。结扎大鼠左冠状动脉前降支（LAD），建立AMI动物模型。模型制备成功后，在环绕LAD周围注射MK为MK干预组。4周后，对大鼠行血流动力学指标检测，称重，计算全心体重指数；取组织制备标本，Masson染色鉴定胶原生成情况；免疫组化检测心肌微血管；TUNEL检测细胞凋亡数；Westernblot分析左心室内Bel-2蛋白、P—ERK1蛋白含量的表达。结果MK组大鼠心功能较AMI组得到明显的改善（P〈0．05）；全心体重指数较AMI组明显降低（3．788±0．630比4．725±0．610，P〈0．05）。sham组与Control组几乎无胶原形成，而AMI组与MK组有明显的胶原组织。在梗死及梗死周边区微血管数目MK组多于AMI组（30．662±1．794比15．275±0．389，P〈0．05），心肌细胞凋亡率明显低于AMI组（27．2±3．2比47．8±4．5，P〈0．05）。MK组Bcl-2蛋白表达较AMI组增多（1．8748±1．0406比1．3637±0．2528，P〈0．05），P—ERK1蛋白表达较AMI组增多（1．2751±0．6353比0．7862±0．5470，P〈0．05）。结论MK对大鼠心梗后心室重塑产生保护作用，其机制可能与MK上调了P—ERK1蛋白表达有关。

Midkine prevents ventricular remodeling in rats with acute myocardial infarction

Objective Observe the influence of midkine （MK） to ventricular remodeling in rats with acute myocardial infarction （AMI）. Methods Forty-eight adult male Wistar rats were randomly divided into four groups： Control group, sham-operated group, infarct model group（AMI group）, MK treatment group （MK group）. AMI model was established by ligation of left anterior descending coronary artery （LAD）. Rats in MK group were injected immediately MK around the LAD after myocardial infarction. Four weeks later, the survived rats were detected haemodynamics, weighed, calculated the whole heart body mass index and prepared specimens. Routine Masson＇s staining were performed to analyze collagen accumulation. staining was carried out in rat heart to quantify neovascularization. Cell apoptosis were tested by TUNEL, Bcl-2, P-ERK1 expression in heart was analyzed by Western blot. Results MK group animals had better cardiac function compared with AMI animals （P〈0.05）. AMI group animals had higher the whole heart body mass index （4.725±0.610）compared with MK animals（3.788±0.630）（P〈0.05）. Sham group and Control group almost no collagen formation, and AMI group and MK group have obvious collagen formation.MK animals had higher vascular density （30.662±1.794） infarction area and border-zone area compared with AMI animals（15.275±0.389） （P〈0.05）. MK animals have less cell apoptosis rate than AMI animals （ 27.2 ± 3.2 ） % vs （47.8 ±4.5 ） % （P〈 0.05 ）. MK animals had strongly upregulated levels of Bcl-2 （ 1.8748± 1.0406 ） compared with AMI animals （ 1.3637 ±0.2528 ） （P〈0.05）. MK animals had strongly upregulated levels of and pho-sphorylated extraceUular signal-regulated kinase （P-ERK1） （ 1.2751±0.6353 ）compared with AMI animals（0.7862±0.5470） （P〈0.05）. Conclusion MK prevents ventrlcular remodeling in rats with acute myocardial infarction, most likely through upregulation of P- ERK1.