Objective: To investigate the effect and mechanism of morroniside on angiogenesis in rats with acute myocardial infarction (AMI) by regulating proteins related to downstream extracellular signal-regulating enzymes 1 and 2 (ERK1/2) signaling pathways through angiogenic growth factor and its vascular endothelial growth factor (VEGF).Methods: Fifty-five SPF-grade healthy adult male SD rats were selected to establish an AMI model by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a sham operation group, a model group, a low-dose M (45 mg/kg morroniside) group, a medium-dose M (90 mg/kg morroniside) group, and a high-dose M (180 mg/kg morronoside) group. The low-dose M group, medium-dose M group, and high-dose M group were given 45 mg/kg, 90 mg/kg and 70 mg/kg by gavage once a day for 2 weeks, respectively. The sham operation group and the model rats were treated with the same amount of distilled water by gavage once a day for 2 weeks. On the seventh day, 5 rats in each group were sacrificed. Their myocardial tissues were taken to compare the density of new small blood vessels, pro-angiogenic growth factors [angiogenin-1 (Ang-1), fibroblast growth factor-2 (FGF-2), and VEGF], and protein expression levels of VEGF downstream ERK1/2 signaling pathway-related factors [p-Src, Src, p-PKC, protein kinase C (PKC), p-ERK1/2, and ERK1/2] in the myocardial tissue of rats in each group. At 14 d, 6 rats in each group were sacrificed, and the blood vessel density around the infarction of each group was compared. Results: After 7 days, the density of a-SMA(+) arterioles in the model group was significantly higher than that in the sham operation group (P<0.05). The a-SMA+ arteriole density of rats in the middle-dose M group and the high-dose M group was significantly higher than that of the model group (P<0.05). After 14 days, the lectin+ vessel density around the infarction in the model group was significantly lower than that in the sham operation group (P<0.05). The density of lectin+ blood vessels around infarction in the high-dose M group was significantly higher than that in the model group (P<0.05). After 7 days, the expression level of Ang-1 protein in the ischemic myocardium of the model group was significantly higher than that of the sham operation group (P<0.05). There was no significant difference in the level of FGF-2 protein in the ischemic myocardium of the model group compared with the sham operation group (P>0.05). The expression levels of Ang-1 and FGF-2 in the ischemic myocardium of rats in the high-dose M group were significantly higher than those in the model group (P<0.05). The expression level of VEGF protein in the ischemic myocardium of the model group was significantly higher than that of the sham operation group. The expression levels of p-Src, p-PKC and p-ERK1/2 in the ischemic myocardium of the model group were not significantly different from those in the sham operation group (P>0.05). The expression levels of VEGF, p-Src, p-PKC and p-ERK1/2 in the ischemic myocardium of rats in the high-dose M group were significantly higher than those in the model group (P<0.05). Conclusion: Morroniside can effectively promote angiogenesis in rats with acute myocardial infarction. Its mechanism of action may be achieved by regulating pro-angiogenic growth factors and related proteins in the downstream ERK1/2 signaling pathway of VEGF.
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