通过调控心脏神经生长因子和Semaphorin3a的平衡表达抑制大鼠心肌梗死后心功能恶化  

The cardiac function deterioration after myocardial infarction was inhibited by regulating the balance expression of cardiac nerve growth factor and Semaphorin3a

作　　者：王海雄 李泽锴 林亚如 李军 李娜 张安欣 孙跃辉 郭李平 余星燕 向杰 Wang Haixiong;Li Zekai;Lin Yaru;Li Jun;Li Na;Zhang Anxin;Sun Yuehui;Guo Liping;Yu Xingyan;Xiang Jie(Department of Cardiology,Shanxi Cardiovascular Hospital,Taiyuan 030024,China;Clinical Medical School of Shanxi Medical University,Taiyuan 030012,China;Academy of Medical Sciences,Shanxi Medical University,Taiyuan 030012,China)

机构地区：[1]山西省心血管病医院心内科,太原030024 [2]山西医科大学临床医学院,太原030012 [3]山西医科大学医学科学院,太原030012

出　　处：《实用医技杂志》2025年第1期5-10,I0001,共7页Journal of Practical Medical Techniques

基　　金：山西省自然科学基金项目(20210302123346)。

摘　　要：目的探索大鼠心肌梗死后交感神经再生和重塑,人为调控相关因子以期减少心肌梗死后病理性重塑所引发的心功能减退,为以后研发有相应效应和特点的抗心力衰竭新药做理论准备。方法利用CRISPR/Cas9和基因敲入技术建立3种大鼠品系模型,与野生型C57BL/6J心肌梗死大鼠比较,在此基础上结扎冠状动脉造成心肌梗死,人为调控心肌梗死后心肌细胞神经生长因子(NGF)和Semaphorin 3a(Sema3a)的动态平衡表达,并利用关键基因表达水平、病理切片观察、心脏超声等方法观察大鼠的心肌病理性重塑和心功能改变。结果与野生型假手术组相比,野生型心肌梗死组大鼠的收缩压(SBP)、舒张压(DBP)、左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)降低(P<0.05),心脏质量/体质量比(HW/BW)增加(P<0.05)。与NGF-Sema3a大鼠假手术组相比,NGF-Sema3a心肌梗死组大鼠的SBP、DBP、平均动脉压(MBP)、LVIDs降低(P<0.05);和野生型大鼠相比,NGF-Sema3a心肌梗死组大鼠的LVIDd、LVIDs降低(P<0.001),左心室缩短分数(FS)、射血分数(EF)升高(P<0.05)。与野生型心肌梗死组相比,NGF-Sema3a心肌梗死组大鼠HW/BW降低(P<0.05),梗死区较小,炎症反应较轻,细胞轮廓较清楚。结论通过调控心肌细胞中的NGF和Sema3a的动态平衡表达可减少心肌梗死面积、减轻心肌炎症和纤维化、降低死亡率、改善心功能。Objective To explore the regeneration and remodeling of sympathetic nerve in mice after myocardial infarction,and to artificially regulate related factors in order to reduce the cardiac dysfunction caused by pathological remodeling after myocardial infarction,so as to make theoretical preparation for the development of anti-heart failure new drugs with corresponding effects and characteristics.Methods Three mouse strain models were established using CRISPR/Cas9 and gene knockout technology.Compared with wild-type C57BL/6J myocardial infarction mice,coronary artery ligation caused myocardial infarction,and nerve growth factor was artificially regulated after myocardial infarction.Dynamic balance expression of nerve grouth factor(NGF)and Semaphorin 3a(Sema3a)was observed.The expression levels of key genes,pathological section observation and cardiac ultrasound were used to observe the rational remodeling and cardiac function changes in mice with cardiomyopathy.Results Compared with the wild-type sham operation group,the systolic blood pressure(SBP),diastolic blood pressure(DBP),left ventricular end-diastolic diameter(LVIDd)and left ventricular end-systolic diameter(LVIDs)in wild-type MI group were decreased(P<0.05),and the ratio of heart to body weight(HW/BW)was increased(P<0.05).SBP,DBP,MBP and LVIDs in NGF-Sema3a group were decreased compared with those in NGF-Sema3a group(P<0.05).Compared with wild-type mice,LVIDd and LVIDs in NGF-Sema3a MI group were decreased(P<0.001),and left ventricular shortening fraction(FS)and ejection fraction(EF)were increased(P<0.05).Compared with wild-type MI group,the HW/BW in NGF-Sema3a MI group was decreased(P<0.05),the infarct area was smaller,the inflammatory reaction was lighter,and the cell profile was clearer.Conclusion Regulating the homeostasis of NGF and Sema3a in cardiomyocytes can reduce myocardial infarction area,alleviate myocardial inflammation and fibrosis,reduce mortality and improve cardiac function.

关 键 词：心肌梗死 心脏功能试验 Semaphorin 3a 神经生长因子 心力衰竭 

分 类 号：R542.22[医药卫生—心血管疾病]