Effects And Mechanisms Of Morroniside On Angiogenesis After Acute Myocardial Infarction In Rats

Objective: To observe the effect of morroniside on angiogenesis and cardiac function in acute myocardial infarction(AMI)rats,and preliminarily explore the possible mechanism to promote angiogenesis.Method:The rat model of AMI was established by ligating the left anterior descending coronary arteries of male Sprague-Dawley rats.The animals were then randomly divided into five groups: sham-operated group,model group and morroniside-low group(45 mg/kg),morroniside-middle group(90 mg/kg),morroniside-high group(180 mg/kg).The sham-operated group was only wearing line without ligation.After the preparation of AMI model,morroniside-treated groups were administered intragastrically once a day with morroniside at the doses of 45 mg/kg,90 mg/kg or 180 mg/kg,while sham-operated group and model group received an equal volume of distilled water.The experimental samples were collected 7 days,14 days and 28 days after AMI,respectively.Angiogenesis and arteriogenesis in the infarct border zone were detected by immunofluorescence of lectin/Ki67 and a-SMA.Vessel density in the infarct border zone was detected by immunofluorescence of lectin.Furthermore,the expressions of FGF-2,Ang-1,VEGFA,and the phosphorylation level of p-Src,p-PKC,p-Erk1/2 were examined by western blot,respectively.The heart function of rats was detected by high resolution small animal ultrasound imaging system(Vevo2100).Result:(1)At 7 days after AMI,compared with sham-operated group,regenerated endothelial cells and newly formed arteries were significantly increased in the infarct border zone,meanwhile the expressions of FGF-2,Ang-1 and Erk1/2 signaling pathway-related proteins VEGFA,p-Src,p-PKC and p-Erk1/2 were increased,respectively.Compared with the model group,morroniside treatment significantly stimulated the generation of vessels and arteries,as well as increased the expression of FGF-2,Ang-1 and Erk1/2 signaling pathway-related proteins VEGFA,p-Src,p-PKC and p-Erk1/2.(2)At 7,14 days after AMI,compared with the sham-operated group,the vessel density in the infarct border zone was reduced.Compared with the model group,morroniside treatment significantly increased the vessel density 14 days after AMI in the infarct border zone.(3)At 14,28 days after AMI,compared with sham-operated group,model group showed lower ejection fraction(EF)and shortening fraction(FS)levels respectively,indicating impaired cardiac function.Compared with model group,morroniside treatment improved EF and FS levels effectively,and left ventricular ejection blood function was improved significantly.Conclusion:(1)Morroniside can promote angiogenesis in the infarcted border zone of rats with acute myocardial infarction,and its effect on improving cardiac function in rats may be related to angiogenesis.(2)Pro-angiogenic factors such as FGF-2,Ang-1 and Erk1/2 of VEGF downstream signal pathway-related proteins VEGFA,p-Src,p-PKC and p-Erk1/2 might mediate the effect of morroniside on angiogenesis in rats with acute myocardial infarction.