衰老蛋白p66^(Shc)在成年小鼠心肌组织修复中的研究  

Study of senescence protein p66^(Shc) on myocardial tissue repair in adult mice

作　　者：张源[1] 黄成珍 陈厚早[2] 聂宇 胡苗清 ZHANG Yuan;HUANG Cheng-Zhen;CHEN Hou-Zao;NIE Yu;HU Miao-Qing(National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine,Fuwai Central China Cardiovascular Hospital,Central China Branch of National Center for Cardiovascular Diseases,Zhengzhou University,Zhengzhou 450046,China;Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China;State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing 100037,China)

机构地区：[1]郑州大学,国家心血管病中心华中分中心,阜外华中心血管病医院,国家卫生健康委员会心血管再生医学重点实验室,郑州450046 [2]中国医学科学院北京协和医学院基础学院,北京100005 [3]中国医学科学院阜外医院心血管疾病国家重点实验室,北京100037

出　　处：《生理学报》2023年第6期946-952,共7页Acta Physiologica Sinica

基　　金：supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CAMS-I2M,2021-I2M-1-072)。

摘　　要：本研究组前期研究显示衰老蛋白p66^(Shc)在新生小鼠心肌再生的过程中发挥着重要的作用,p66^(Shc)缺失会导致新生小鼠受损心肌再生能力减弱。本文旨在探讨p66^(Shc)蛋白在成年小鼠心肌梗死(简称心梗)后心肌损伤修复中的作用,以期为心梗后心肌损伤治疗提供新的靶点。通过前降支结扎手术构建成年野生型(WT)和p66^(Shc)敲除(KO)小鼠心梗模型,比较分析两种小鼠心梗术后的生存率和心重体重比,用Masson染色检测受损心肌瘢痕化面积,用麦胚凝集素(wheat germ agglutinin, WGA)染色测定小鼠心梗后心肌细胞面积,用TUNEL染色检测心肌细胞的凋亡程度,用Western blotting检测心肌肥厚常用标志物脑利尿钠肽(brain natriuretic peptide, BNP)的表达变化。结果显示,与野生型小鼠相比,p66^(Shc)KO小鼠心梗术后的生存率、心肌瘢痕化面积、心肌细胞凋亡、心重体重比无显著差异,而BNP蛋白表达水平下调。以上结果提示,与新生小鼠不同,衰老蛋白p66^(Shc)的缺失对成年小鼠心梗后心肌损伤修复没有显著作用。Our previous study has shown that p66^(Shc) plays an important role in the process of myocardial regeneration in newborn mice,and p66^(Shc) deficiency leads to weakened myocardial regeneration in newborn mice.This study aims to explore the role of p66^(Shc) protein in myocardial injury repair after myocardial infarction in adult mice,in order to provide a new target for the treatment of myocardial injury after myocardial infarction.Mouse myocardial infarction models of adult wild-type(WT)and p66^(Shc) knockout(KO)were constructed by anterior descending branch ligation.The survival rate and heart-to-body weight ratio of two models were compared and analyzed.Masson's staining was used to identify scar area of injured myocardial tissue,and myocyte area was determined by wheat germ agglutinin(WGA)staining.TUNEL staining was used to detect the cardiomyocyte apoptosis.The protein expression of brain natriuretic peptide(BNP),a common marker of myocardial hypertrophy,was detected by Western blotting.The results showed that there was no significant difference in survival rate,myocardial scar area,myocyte apoptosis,and heart weight to body weight ratio between the WT and p66^(Shc)KO mice after myocardial infarction surgery.Whereas the protein expression level of BNP in the p66^(Shc)KO mice was significantly down-regulated compared with that in the WT mice.These results suggest that,unlike in neonatal mice,the deletion of p66^(Shc) has no significant effect on myocardial injury repair after myocardial infarction in adult mice.

关 键 词：p66^(Shc) 成年小鼠 心肌梗死模型 心肌梗死修复 

分 类 号：R542.22[医药卫生—心血管疾病] R-332[医药卫生—内科学]