2022版加拿大实验动物管理委员会(Canadian Council On Animal Care,CCAC)动物人道终点指南——《动物科学终点、人道干预点和累积终点确定指南》(Identification of Scientific Endpoints,Humane Intervention Points,and Cumulative E...2022版加拿大实验动物管理委员会(Canadian Council On Animal Care,CCAC)动物人道终点指南——《动物科学终点、人道干预点和累积终点确定指南》(Identification of Scientific Endpoints,Humane Intervention Points,and Cumulative Endpoints)简称“指南”)根据最新的研究文献,对现有的实验动物人道终点理论进行了补充和拓展。本文总结了该指南的主要内容,对动物实验的科学终点、人道干预点、累积终点的确定、实施和监督进行了阐述和分析,以期为同行提供有益的参考和借鉴。展开更多
SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate...SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate the functional significance of deacetylase activity of SIRT1 in heart.Here we show that the early postnatal hearts expressed the highest level of SIRT1deacetylase activity compared to adult and aged hearts.We generated transgenic mice with cardiac-specific expression of a dominant-negative form of the human SIRT1(SIRT1H363Y),which represses endogenous SIRT1 activity.The transgenic mice displayed dilated atrial and ventricular chambers,and died early in the postnatal period.Pathological,echocardiographic and molecular phenotype confirmed the presence of dilated cardiomyopathy.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis revealed a greater abundance of apoptotic nuclei in the hearts of transgenic mice.Furthermore,we show that cardiomyocyte apoptosis caused by suppression of SIRT1 activity is,at least in part,due to increased p53acetylation and upregulated Bax expression.These results indicate that dominant negative form of SIRT1(SIRT1H363Y)overexpression in mouse hearts causes cardiomyocyte apoptosis and early-onset heart failure,suggesting a critical role of SIRT1 in preserving normal cardiac development during the early postnatal period.展开更多
文摘2022版加拿大实验动物管理委员会(Canadian Council On Animal Care,CCAC)动物人道终点指南——《动物科学终点、人道干预点和累积终点确定指南》(Identification of Scientific Endpoints,Humane Intervention Points,and Cumulative Endpoints)简称“指南”)根据最新的研究文献,对现有的实验动物人道终点理论进行了补充和拓展。本文总结了该指南的主要内容,对动物实验的科学终点、人道干预点、累积终点的确定、实施和监督进行了阐述和分析,以期为同行提供有益的参考和借鉴。
基金supported by the National Natural Science Foundation of China(31271227,81161120551)the National Basic Research Program of China(2011CB503902)
文摘SIRT1,a mammalian ortholog of yeast silent information regulator 2(Sir2),is an NAD+-dependent protein deacetylase that plays a critical role in the regulation of vascular function.The current study aims to investigate the functional significance of deacetylase activity of SIRT1 in heart.Here we show that the early postnatal hearts expressed the highest level of SIRT1deacetylase activity compared to adult and aged hearts.We generated transgenic mice with cardiac-specific expression of a dominant-negative form of the human SIRT1(SIRT1H363Y),which represses endogenous SIRT1 activity.The transgenic mice displayed dilated atrial and ventricular chambers,and died early in the postnatal period.Pathological,echocardiographic and molecular phenotype confirmed the presence of dilated cardiomyopathy.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis revealed a greater abundance of apoptotic nuclei in the hearts of transgenic mice.Furthermore,we show that cardiomyocyte apoptosis caused by suppression of SIRT1 activity is,at least in part,due to increased p53acetylation and upregulated Bax expression.These results indicate that dominant negative form of SIRT1(SIRT1H363Y)overexpression in mouse hearts causes cardiomyocyte apoptosis and early-onset heart failure,suggesting a critical role of SIRT1 in preserving normal cardiac development during the early postnatal period.
