重组人生长激素对急性心肌梗死大鼠冠状动脉侧支循环的影响

Effect of rh-GH on coronary collateral circulation of rats with acute myocardial infarction

目的 :探讨重组人生长激素 (rh GH)对急性心肌梗死 (AMI)大鼠冠状动脉侧支循环及血管内皮细胞生长因子 (VEGF)、成纤维细胞生长因子 (bFGF)的影响。方法 :5 0只Wistar大鼠经 10 %戊巴比妥钠麻醉后开胸 ,剪开心包腔 ,经左冠状动脉前降支结扎术致其发生AMI ,术后 2 4h存活者 37只被随机分为治疗组 (19只 )和对照组 (18只 )。治疗组以rh GH 0 .2 5IU/kg肌内注射 ,对照组肌内注射同等容积的0 .9%氯化钠溶液 ,3周后处死大鼠 ,开胸经升主动脉向冠状动脉内灌注 4 %多聚甲醛 2 0～ 30min固定心脏 ,心脏标本经切片处理。分别测定血浆和心肌的VEGF、bFGF的量及左室毛细血管密度。结果 :治疗组与对照组在AMI后 3周其血浆bFGF、VEGF浓度均较实验开始时明显增加 (P <0 .0 5 )。治疗组较对照组升高更加显著 ,分别为 (6 8.72± 4 .5 7)∶(35 .6 0±4 .31)和 (4 7.0 5± 5 .13)∶(32 .13± 5 .70 ) (均P <0 .0 5 )。大鼠心肌内bFGF及VEGF治疗组均较对照组高 ,分别为 (79.0 5± 6 .96 )∶(30 .7± 3.4 9)和 (72 .0 5± 6 .73)∶(39.33± 6 .78) (均P <0 .0 1)。血浆bFGF、VEGF的浓度与心肌内毛细血管密度呈正相关 (r分别为 0 .91和 0 .86 ,均P <0 .0 1)。结论 :rh

objective:To determine the effect of intramuscular administration of rh-GH on coronary collateral circulation and the expression of bFGF and VEGF in an experimental model rat with acute myocardial infarction(AMI). Method:Left anterior descending coronary arteries were ligated in 50 Wistar rats after anesthesia by 10% pentobarbital sodium. Thirty-seven rats with AMI were survived after operation. Theses rats were randomized into rh-GH treatment group (n=19) and control group (n=18). Treatment group is given rh-GH 0.25 IU·kg -1·d -1, im; control group is given NS im. All the 37 rats were killed after 3 weeks. heart specimens were fixed by injecting 10% formalin from ascending aorta into coronary arteries. Plasma VEGF and bFGF were measured before experiment and 3 weeks after experiment by enzyme-label method. bFGF and VEGF in myocardiun were semi-quaot fixed by imaging after SP inmuno-histochemical stain. Left ventricle capillary density: 3 angiogenesis sites were identified by 40× or 100× microscopy. F 8 labelled microvessels were measured averagely under 200× microscope. Result:Plasma VEGF and bFGF in both group were elevated (P< 0.05),and elevation in treatmert group were more remarkable than control group 47.05± 5.13 vs 32.13± 5.70 (P< 0.05) and 68.72± 4.57 vs 35.60± 4.31 (P< 0.05) respectively. bFGF and VEGF of myocardium in treatment group were higher than that in control group, 79.05± 6.96 vs 30.78± 3.49(P< 0.01) and 72.05± 6.73 vs 39.33± 6.78 (P< 0.01) respectively. The left ventricular capillary density in treatment group were more than that in control group ( 50.95± 6.14 vs 28.56± 2.94,P< 0.01) . Plasma VEGF and bFGF were both positively correlated with left ventricular capillary density(correlatin coefficient are 0.86 and 0.91, P< 0.01 respectively), Regression equations were capillary= 1.249 VEGF+ 6.127and capillary= 1.85 bFGF- 18.526 respectively. Conclusion:rh-GH can increase the expression and excretion of myocardial growth factors VEGF and bFGF, increase VEGF and bFGF content in both ischemic myocardium and systemic circulation, promote the formation of coronary collateral circulation in our experimental models.