咪达唑仑和异丙酚对急性心肌梗死大鼠血清VEGF浓度及G—CSF药物动员骨髓干细胞效果的影响

Effect of midazolam and propofol on serum VEGF concentration and G-CSF-induced bone marrow stem cell mobilization after acute myocardial infarction in rats

目的评价咪达唑仑和异丙酚对急性心肌梗死大鼠血清血管内皮生长因子（VEGF）浓度及粒细胞集落刺激因子（G-CSF）药物动员骨髓干细胞效果的影响。方法雄性Wistar大鼠36只，体重250～280g，采用结扎左冠状动脉前降支的方法制备急性心肌梗死模型，采用腹腔连续注射G-CSF5d进行药物动员，于药物动员后第7天，按照随机数字表法，将大鼠随机分为G-CSF组（G组）、咪达唑仑组（M组）及异丙酚组（P组），每组12只。G组以0．5ml／h的速率股静脉输注生理盐水6h；M组股静脉输注咪达唑仑0．05mg.kg-1·h-1 6h；P组股静脉输注异丙酚5mg·kg-1.h-16h。于给药完毕后经股静脉取血，采用流式细胞仪测定CD34＋单核细胞（CD34＋MNC）和内皮祖细胞（EPCs）数目，采用ELISA法测定血清VEGF浓度。于心肌梗死后4周每组随机取6只大鼠测定左心室舒张末压（LVEDP）、最大收缩速率（＋dp／dtmax）和最大舒张速率（-dp／dt max）。结果与G组比较，M组CD34＋MNC及EPCs细胞数目增加，血清VEGF浓度升高，LVEDP下降，-dp／dtmax，的绝对值升高（P〈0．05），P组LVEDP下降，-dp／dt-的绝对值升高（P〈0．05）；与P组比较，M组CD34＋MNC及EPCs细胞数目增加，血清VEGF浓度升高，LVEDP下降，-dp／dt-的绝对值升高（P〈0．05）。结论咪达唑仑可促进VEGF的释放，加强G-CSF动员骨髓干细胞的作用，改善急性心肌梗死后大鼠的心脏功能；异丙酚不能促进VEGF的释放及无骨髓干细胞动员的作用。

Objective To investigate the effect of propofol and midazolam on the serum vascular endothelial growth factor （VEGF） concentration and granulocyte colony-stimulating factor （G-CSF）-induced bone marrow stem cell （BMSC） mobihzation after acute myocardial infarction in rats. Methods Thirty-six male Wistar rats, weighing 250-280 g, were anesthetized with intraperitonel 1% pentobarbital 45 mg/kg. Acute myocardial infarct was induced by ligation of left anterior descending branch of coronary artery. BMSC mobilization was induced by intraperitoneal injection of G-CSF for 5 days. On 7th day after BMSC mobilization, the rats were equally and ran- domly divided into three groups： G-CSF group （group G）, midazolam group （group M） and propofol group （group P）. In group G, normal saline was continuously infused via the femoral vein at a rate of 0.5 ml/h for 6 h. In group M, midazolam was infused via the femoral vein at 0.05 mg. kg- 1 . h-1 for 6 h. In group P, propofol was infused via the femoral vein at 5 mg. kg- 1. h - 1 for 6 h. Blood samples were obtained from the femoral vein after administration to determine the number of CD34＋ monocyte （CD34 ＋ MNC） and endothelial progenitor cells （EPCs） by flow cytometry and the serum concentration of VEGF by ELISA. Six rats from each group were chosen 4 weeks after myocardial infarction for measurement of the left ventricular end-diastolic pressure （LVEDP） and ± dp/dtmax. Results Compared with group G, the number of CD34 ＋ MNC and EPCs, the serum concentration of VEGF, and the absolute value of - dp/dtmax were significantly increased, while LVEDP was significantly decreased in group （P 〈 0.05 ）, and LVEDP was significantly decreased, and the absolute value of - dp/dtmax, was significantly increased in group P （ P 〈 0.05）. Compared with group P, the number of CD34＋ MNC and EPCs, the serum concentration of VEGF, and the absolute value of - dp/dtmax were significantly increased, while LVEDP was significantly decreased in group M （ P 〈 0.05 ）. Conclusion Midazolam can promote the release of VEGF, strengthen G-CSF-induced BMSC mobilization and improve the cardiac function after acute myocardial infarction in rats. Propofol can not promote the release of VEGF and produce G-CSF-induced BMSC mobilization after acute myocardial infarction in rats.