大剂量乌司他丁对心肌保护作用的实验研究

Study on the efficacy of high-dosage ulinastatin for myocardial protection

目的探讨大剂量乌司他丁对心肌保护作用及其机制。方法 30只日本大耳白兔结扎前降支制作心肌梗死模型,然后随机分为对照组、小剂量组(30 000μ/kg)、大剂量组(60 000μ/kg),连续给药2周,实验前后行心脏超声检查,氯胺T氧化法测定心肌局部组织羟脯氨酸(Hyp),流式细胞仪测定细胞凋亡,评估心肌损伤情况。结果与对照组相比,大、小剂量组均能改善左室射血分数、每搏心输出量等,左室收缩、舒张期末径较治疗前缩小,大剂量组效果更好(P<0.05)。并且大剂量乌司他丁能更好抑制心肌细胞凋亡。应用乌司他丁可明显抑制兔心肌梗死心肌局部组织Hyp含量,其中大剂量组组织Hyp含量最低(P<0.05)。结论大剂量乌司他丁心肌保护作用最强,与抑制心室重塑、心肌间质纤维化及细胞凋亡有关。

Objective To explore the efficacy of high-dosage ulinastatin for myocardial protection and its mechanism.Methods The rabbit model of myocardial infarction had been established by ligation of anterior descending branch of coronary artery in 30 Japanese white rabbits,and they were randomly divided into control group,low dosage ulinastatin group（30 000 μ/kg） and high-dosage ulinatatin group（60 000 μ/kg）,ulinastatin had been continuously administrated for two weeks,and echocardiography was examined before and after the experiment.Hydroxyproline（Hyp） in myocardial tissue was determined by chloramines-T oxidation method,and apoptosis was measured by flow cytometry for assessment of myocardial damage.Results In comparison with control group,cardiac function including LVEF,LVEDD and LVESD had been improved,and myocardial Hyp content and apoptosis： were decreased in medical treatment groups.Conclusion The high-dosage of ulinastatin has the action of myocardial protection and inhibit ventricular remodeling,myocardial interstitial fibrosis and apoptosis.