巴戟天醇提取物促大鼠缺血心肌治疗性血管生成的实验研究

The angiogenic promoting effect of Morinda officinalis How oligosaccharides in the ischemic myocardium of rats after acute myocardial infarction

目的探讨巴戟天糖链(MOO)对急性心肌梗死(AMI)大鼠缺血心肌治疗性血管生成的影响及其机制。方法♂Wistar大鼠,结扎冠状动脉左前降支,成功制成AMI模型40只,随机分为MOO小、中、大剂量组、麝香保心丸组及模型组,每组8只。另取10只建立假手术组。药物治疗组分别灌胃给予巴戟天醇提物水溶性部分(0.7、1.4、2.8mg.kg-1.d-1)及麝香保心丸悬浊液(30mg.kg-1.d-1),其余两组灌胃给予等量蒸馏水。连续灌胃6wk后处死大鼠,心肌取材,应用免疫组织化学法检测大鼠缺血心肌Ⅷ因子及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growthfactor,bFGF)蛋白表达情况;计算微血管密度(microvessecdensity,MVD),用图像分析软件测定VEGF及bFGF表达灰度值,并进行半定量分析。结果与模型组相比,MOO中、大剂量组能增加缺血心肌MVD及VEGF、bFGF灰度值(P<0.05),但作用弱于麝香保心丸组(P<0.05);MOO3个剂量组之间MVD差异均有显著性(P<0.05);MOO3个剂量组之间VEGF灰度值差异均有显著性(P<0.05);MOO中、大剂量组bFGF灰度值与小剂量组相比差异有显著性(P<0.05)。结论MOO可促进AMI后大鼠缺血心肌的血管生成,其机制可能与上调缺血心肌VEGF、bFGF蛋白的表达有关。

Aim To investigate the angiogenic promoting effect of Morinda officinalis How oligosaccharides（MOO）in the ischemic myocardium of rats after acute myocardial infarction（AMI）.Methods 40 male Wistar rats were established into AMI model successfully and were randomly divided into 5 groups equally,i.e.the low,medium and high doses of MOO groups,the Shexiangbaoxin group and the model group.They were treated with different doses of the water fraction of the ethanolic extract of Radix morinda officinalis（0.7,1.4,2.8 mg·kg-1·d-1）,suspension liquid of Shexiangbaoxin Pill（30 mg·kg-1·d-1）and distilled water with the same volume respectively.Besides,a sham operated group with 10 rats was set up for control.All rats were sacrificed after 6-week-treatment.The Ⅷ coagulation factor,vascular endothelial growth factor（VEGF）and basic fibroblast growth factor（bFGF）protein in ischemic myocardium of rats in each group were detected by immunohistochemistry assay.The microvessel density（MVD）was calculated.Gray values of protein expression of VEGF and bFGF in ischemic myocardium were calculated and analyzed by image analysis system.Results The MVD,the gray values of VGF and bFGF were higher in the medium and high doses of MOO groups than those in the model group（P0.05）,but still lower than those in the Shexiangbaoxin group（P0.05）.The MVD and the gray values of VEGF among 3 doses of MOO groups showed significant differences（P0.05）.Significant differences of gray value of bFGF were observed between small and middle doses of MOO groups,also between small and large doses of groups（P0.05）.Conclusion MOO can obviously promote angiogenesis in the ischemic myocardium of the rats after AMI.And up-regulating expressions of VEGF and bFGF protein in the ischemic myocardium may act as one of its angiogenic promoting mechanisms.