Impacts of pachymic acid on myocardial injury in rats with acute myocardial infarction by regulating the CCL2-CCR2 signaling pathway
Objective To investigate the impacts of pachymic acid on myocardial injury in rats with acute myocardial infarction(AMI),and the role of the monocyte chemoattractant protein-1/CC-motif chemokine ligand 2(MCP-1/CCL2)-chemokine receptor 2(CCR2)signaling pathway.Methods The AMI rat model was established by ligation of the left anterior descending branch,and the rats were grouped into model groups,and low-dose,medium-dose and high-dose pachymic acid groups,with 15 rats in each group.Another 15 rats were taken as the sham operation group.After 14 days of drug intervention,indicators associated with cardiac function were detected using a small animal ultrasound system.The enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors.The hematoxylin and eosin(H&E)staining was applied to detect pathological damage in myocardial tissue.The terminal deoxynucleotidyl transferase dUTP nick end-labeling(TUNEL)staining was applied to observe the apoptosis of cardiomyocytes.Western blot was applied to detect the protein levels of CCL2,CCR2,and Caspase-3 in myocardial tissue.Results Compared with those of the sham surgery group,rats in the model group presented severe damages to the rat myocardium,massive infiltration of inflammatory cells,significantly higher indicators associated with cardiac function like the left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVESD),serum levels of inflammatory factors(interleukin 6[IL-6],tumor necrosis factor-alpha[TNF-α]and interleukin-1beta[IL-1β]),TUNEL positive rate of myocardial cells,and protein levels of CCL2,CCR2 and Caspase-3 in myocardial tissues and significantly lower left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)(P<0.05).Compared with those of the model group,rats in low-dose,medium-dose and high-dose pachymic acid groups presented gradually recovered myocardium,alleviated infiltration of inflammatory cells,significantly decreased LVEDD,LVESD,serum levels of IL-6,TNF-α and IL-1β,TUNEL positive rate of myocardial cells,and protein levels of CCL2,CCR2 and Caspase-3 in myocardial tissues and significantly higher LVEF and LVFS in a dose-dependent manner(P<0.05).Conclusion Pachymic acid may alleviate myocardial injury in AMI rats by regulating the CCL2-CCR2 signaling pathway.