Netrin-1 improves ventricular remodeling in rats with myocardial infarction through the DCC/ERK signaling pathway
Objective To investigate the effect of netrin-1 on ventricular remodeling in rats with myocardial infarction and its mechanism.Methods Rats were randomly divided into sham group(sham),myocardial infarction model group(AMI),myocardial infarction+netrin-1 low-dose group(low-dose),myocardial infarction+netrin-1 high-dose group(high-dose),8 rats in each group.The rat model of acute myocardial infarction was established and treated with intraperitoneal injection of netrin-1 for 4 weeks.The changes of cardiac function indexes in rats was detected.The myocardial histopathological changes was observed by HE staining.The myocardial fibrosis in rats was observed by masson staining.The apoptosis of cardiomyocytes was detected by TUNEL staining.The expressions of DCC,ERK1/2 and p-ERK1/2 were detected by Western blot.Results Compared with the AMI group,the maximum rate of rise and fall(±dp/dtmax)of left ventricular systolic blood pressure(LVSP)and left ventricular pressure in the low and high dose group of netrin-1 was significantly increased,and the value of left ventricular end-diastolic blood pressure(LVEDP)was significantly reduced.Rats had significant decreases in cardiac mass/body mass(HW/BW),(left ventricle+ventricular septum)mass/body mass[(LV+S)/BW],and(left ventricle+ventricular septum)mass/heart mass[(LV+S)/HW].Cardiomyocyte necrosis,inflammatory cell infiltration and collagen deposition was all reduced.The number of apoptotic cardiomyocytes was significantly reduced.The levels of DCC and p-ERK1/2 proteins were significantly increased.Conclusion Netrin-1 can significantly improved ventricular remodeling in rats with myocardial infarction,and its mechanism of action may be related to the activation of DCC/ERK signaling pathway.
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