Objective:To explore the post-infarction sympathetic nerve regeneration and remodeling in mice,and to artificially regulate the related factors in order to reduce the fatal arrhythmias and sudden cardiac death(SCD) triggered by post-infarction sympathetic nerve pathological remodeling.Methods:Three mouse strain models were established using techniques such as CRISPR/Cas9 and knock-in to compare with wild-type C57BL/6J infarction mice,based on these models coronary arteries were ligated to cause infarction,and the dynamic and balanced expression of nerve growth factor ( NGF) and Semaphorin 3a ( Sema3a) was artificially regulated in myocardial cells after myocardial infarction. Results:Compared with wild type sham operation group,systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MBP) in wild type myocardial infarction group were decreased(P<0.05),and left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),heart/body weight ratio(HW/BW) were increased(P<0.05).SBP,DBP,MBP in NGF-Sema3a infarction group were decreased and LVESD was increased compared with those in NGF-Sema3a sham operation group (P<0.05). Compared with wild-type mice,LVEDD and LVESD of NGF-Sema3a myocardial infarction group were decreased (P<0.001),left ventricular fraction shortening ( FS) and ejection fraction ( EF) were increased(P<0.05).Compared with wild-type myocardial infarction group,the HW/BW in NGF-Sema3a myocardial infarction group was decreased(P<0.05),the infarct area was smaller,the inflammatory reaction was lighter,and the cell profile was clearer. Conclusion:By regulating the dynamic and balanced expression of NGF and Sema3a in myocardial cell can reduce infarct size,attenuate myocardial inflammation and fibrosis,decrease mortality,and improve cardiac function.
关键词
心源性猝死/心肌梗死/心律失常/信号素3A/神经生长因子/实验研究
Key words
sudden cardiac death/myocardial infarction/arrhythmia/Semaphorin 3a/nerve growth factor/experimental study
维普
万方数据