前列腺素E1促进大鼠急性心肌梗死模型血管内皮生长因子表达及量效关系研究

目的 探讨前列腺素E1（PGE1）对急性心肌梗死（AMI）大鼠心肌血管生成及血管内皮生长因子（VEGF）表达的影响，以及PGE1剂量与心肌细胞分泌VEGF蛋白之间的初步量效关系。方法SD大鼠经10％戊巴比妥钠麻醉后，开胸结扎冠脉左前降支，建立大鼠AMI模型。PGE1治疗各亚组应用不同剂量PGE1每日静脉注射，分别在手术后2周和4周处死大鼠，取心脏标本切片，HE染色及VEGF、CD34免疫组化染色后显微镜观察。定量分析心肌VEGF蛋白水平及毛细血管密度，并测定血浆VEGF蛋白浓度。结果 PGE1治疗组VEGF蛋白的表达、毛细血管密度、血浆VEGF浓度显著增加，明显高于对照组和假手术组（均P〈0．05）。随PGE1剂量的增加，VEGF蛋白水平相应升高。但PGE1治疗组各亚组之间毛细血管密度无明显差异（P〉0．05）。结论前列腺素E1可以增加AMI大鼠心肌VEGF蛋白表达和梗死区域毛细血管密度，促进侧支循环建立。前列腺素E1引起的心肌VEGF蛋白表达升高作用呈剂量依赖性，前列腺素E1剂量与心肌细胞分泌VEGF蛋白之间具有一定量效关系。

Effects of PGE1 on the expression of VEGF in rat cardiac myocytes and dose-effect relationship between PGE1 and the expression of VEGF

Objective To determine the effect of intravascular administration of prostaglandin E1(PGE1) on myocardial angiogenesis and the expression of vascular endothelial growth factor(VEGF) in rats with acute myocardial infarction,and the relationship between the dose of intravascular administration of PGE1 and the effect of expression of VEGF in rat cardiac myocytes.Methods Left anterior descending coronary arteries were ligated in SD rats after anesthesia by 10% pentobarbital sodium.Treatment group was given various doses of PGE1 intravenously for 2 and 4 weeks while the control group and the sham-operation group were given normal saline(NS) intravenously at the same time.All the rats were killed and the heart specimen were fixed by 10% formalin,sectioned and colorated by means of HE staining and immunohistochemical staining to observe VEGF and CD34 through microscope,which were quantified with the help of computer assisted morphometry.The levels of VEGF in plasma were measured before experiment,2 and 4 weeks after experiment by enzyme-linked immuno-sorbent assay(ELISA) respectively.Results PGE1 treated group had significantly higher levels of VEGF protein expression in the myocardium as compared to the control group and the sham-operation group(all P<(0.05).) Meanwhile there was a significant increase in the number of capillaries in the PGE1 treated group when compared with the other 2 groups(all P<0.05).The VEGF producing in cardiac myocytes increased responsively with the increase of the dose of intravascular administration of PGE1.But there was no significant difference in the number of capillaries among PGE1-treated subgroups.Conclusions PGE1 can increase the excretion of VEGF and the number of capillaries,and enhance collateral circulation of the occluded coronary.PGE1 can stimulate the expression and excretion of VEGF in cardiac myocytes in a dose-dependent manner.