目的探讨心肌肥厚性重构可能分子机制。方法选取8周龄清洁级雄性C57小鼠18只,随机分为升主动脉缩窄术(TAC)组和对照组(SHAM组),每组9只。TAC组给予升主动脉缩窄术(TAC术)构建心肌肥厚模型。SHAM组给予假手术。术后4周,利用二氧化碳窒息...目的探讨心肌肥厚性重构可能分子机制。方法选取8周龄清洁级雄性C57小鼠18只,随机分为升主动脉缩窄术(TAC)组和对照组(SHAM组),每组9只。TAC组给予升主动脉缩窄术(TAC术)构建心肌肥厚模型。SHAM组给予假手术。术后4周,利用二氧化碳窒息处死实验小鼠,剖开胸腔后分离心脏组织,用于后续实验。H&E染色观察心脏组织结构;心室/体质量指数评估心室重构情况;荧光测定法测定心脏组织中组蛋白去乙酰化酶(HDACs)活性;qPCR检测MYH7、PDE4b、HDAC4、HDAC5及HDAC9的表达水平,Western blot检测PDE4b及HDAC9蛋白表达水平,ChIP-qPCR检测HDAC9与PDE4b启动子结合水平。结果与SHAM组相比,TAC组小鼠室间隔及左室壁明显增厚,心室/体质量指数明显升高(4.48±0.18 vs 5.50±0.23)(P<0.05),心肌肥厚标志物MYH7表达明显升高(0.91±0.04 vs 1.44±0.07)(P<0.05);PDE4b表达明显降低(mRNA水平0.75±0.09 vs 0.27±0.06;蛋白水平0.67±0.11 vs 0.34±0.05)(P<0.05);肥厚心肌组织中组蛋白去乙酰化酶活性显著增加(3.24±0.32 vs 5.03±0.58)(P<0.05),HDAC9表达显著升高(mRNA水平0.85±0.08 vs 1.35±0.07;蛋白水平0.77±0.10 vs 1.25±0.05)(P<0.05),而HDAC4、HDAC5表达与SHAM组无明显差异(P>0.05);HDAC9与PDE4b启动子结合水平明显升高(1.67±0.10 vs 2.47±0.20)(P<0.05)。结论心肌肥厚中HDAC9可能参与下调PDE4b表达,进而参与心室肌肥厚性重构。展开更多
This study was conducted to explore the potential of plant-based food materials as reservoirs of natural active compounds for the management and prevention of respiratory diseases focusing on relief of symptoms includ...This study was conducted to explore the potential of plant-based food materials as reservoirs of natural active compounds for the management and prevention of respiratory diseases focusing on relief of symptoms including inflammation and cough.Herein,this research suggests the dietary choices that incorporate active compounds capable of targeting various respiratory symptoms simultaneously.To identify active compounds that regulate respiratory symptoms by targeting N-methyl-D-aspartate receptor(NMDAR)and Phosphodiesterase-4B(PDE4B),we adopted a systemic process integrated with machine learning.Through this process,the active compounds and food materials were predicted in an efficient manner.Additionally,we propose potential applications for drug candidate discovery and suggest assessing toxicity and safety through inter-material interactions.展开更多
文摘目的探讨心肌肥厚性重构可能分子机制。方法选取8周龄清洁级雄性C57小鼠18只,随机分为升主动脉缩窄术(TAC)组和对照组(SHAM组),每组9只。TAC组给予升主动脉缩窄术(TAC术)构建心肌肥厚模型。SHAM组给予假手术。术后4周,利用二氧化碳窒息处死实验小鼠,剖开胸腔后分离心脏组织,用于后续实验。H&E染色观察心脏组织结构;心室/体质量指数评估心室重构情况;荧光测定法测定心脏组织中组蛋白去乙酰化酶(HDACs)活性;qPCR检测MYH7、PDE4b、HDAC4、HDAC5及HDAC9的表达水平,Western blot检测PDE4b及HDAC9蛋白表达水平,ChIP-qPCR检测HDAC9与PDE4b启动子结合水平。结果与SHAM组相比,TAC组小鼠室间隔及左室壁明显增厚,心室/体质量指数明显升高(4.48±0.18 vs 5.50±0.23)(P<0.05),心肌肥厚标志物MYH7表达明显升高(0.91±0.04 vs 1.44±0.07)(P<0.05);PDE4b表达明显降低(mRNA水平0.75±0.09 vs 0.27±0.06;蛋白水平0.67±0.11 vs 0.34±0.05)(P<0.05);肥厚心肌组织中组蛋白去乙酰化酶活性显著增加(3.24±0.32 vs 5.03±0.58)(P<0.05),HDAC9表达显著升高(mRNA水平0.85±0.08 vs 1.35±0.07;蛋白水平0.77±0.10 vs 1.25±0.05)(P<0.05),而HDAC4、HDAC5表达与SHAM组无明显差异(P>0.05);HDAC9与PDE4b启动子结合水平明显升高(1.67±0.10 vs 2.47±0.20)(P<0.05)。结论心肌肥厚中HDAC9可能参与下调PDE4b表达,进而参与心室肌肥厚性重构。
基金supported by the Korean Institute of Planning and Evaluation for Technology in Food,Agriculture and Forest(IPET)through the High Value-added Food Technology Development Program,funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA)(321029-05)Brain Korea 21 Plus Program of the Department of Agricultural Biotechnology,Seoul National University,Republic of Korea.
文摘This study was conducted to explore the potential of plant-based food materials as reservoirs of natural active compounds for the management and prevention of respiratory diseases focusing on relief of symptoms including inflammation and cough.Herein,this research suggests the dietary choices that incorporate active compounds capable of targeting various respiratory symptoms simultaneously.To identify active compounds that regulate respiratory symptoms by targeting N-methyl-D-aspartate receptor(NMDAR)and Phosphodiesterase-4B(PDE4B),we adopted a systemic process integrated with machine learning.Through this process,the active compounds and food materials were predicted in an efficient manner.Additionally,we propose potential applications for drug candidate discovery and suggest assessing toxicity and safety through inter-material interactions.
