目的:探讨睾酮改善心力衰竭可能的分子生物学机制。方法:建立心衰模型,将大鼠随机分为假手术组、心衰组和睾酮干预组(给予生理剂量的睾酮补充),3个月后处死动物,取心脏,2剥离左心室,用半定量RT-PCR检测心肌组织中SERCA-2 a mRNA含量的...目的:探讨睾酮改善心力衰竭可能的分子生物学机制。方法:建立心衰模型,将大鼠随机分为假手术组、心衰组和睾酮干预组(给予生理剂量的睾酮补充),3个月后处死动物,取心脏,2剥离左心室,用半定量RT-PCR检测心肌组织中SERCA-2 a mRNA含量的变化。结果:睾酮干预组SERCA-2 a mRNA相对表达量较心衰组升高(0.516±0.075 vs 0.428±0.062,P<0.05),但依然低于假术手组(0.516±0.075 vs 0.572±0.063,P<0.05)。结论:睾酮可使心肌组织SERCA-2 amRNA含量上升,睾酮补充疗法可能是改善心衰的分子机制之一。展开更多
目的:探讨睾酮改善心力衰竭(心衰)可能的分子生物学机制。方法:将SD大鼠随机分为假手术组、心衰组和心衰睾酮干预组(给予生理剂量的睾酮补充),后2组建立心衰模型,饲养观察3个月后处死动物,取心脏,剥离左心室,用半定量RT-PCR检测心肌组织...目的:探讨睾酮改善心力衰竭(心衰)可能的分子生物学机制。方法:将SD大鼠随机分为假手术组、心衰组和心衰睾酮干预组(给予生理剂量的睾酮补充),后2组建立心衰模型,饲养观察3个月后处死动物,取心脏,剥离左心室,用半定量RT-PCR检测心肌组织中Fas、SERCA-2a mRNA含量的变化。结果:睾酮干预组FasmRNA相对表达量较心衰组显著降低(0.535±0.041 vs 0.570±0.060,P<0.05),但仍高于假手术组(0.431±0.056,P<0.05);睾酮干预组SERCA-2amRNA相对表达量较心衰组升高(0.516±0.075 vs 0.428±0.062P<0.05),但依然低于假术手组(0.572±0.063,P<0.05)。结论:睾酮可使心肌组织Fas含量下降、SERCA-2a mRNA含量上升,睾酮补充疗法可能是改善心衰的分子机制之一。展开更多
Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in ...Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.展开更多
文摘目的:探讨睾酮改善心力衰竭可能的分子生物学机制。方法:建立心衰模型,将大鼠随机分为假手术组、心衰组和睾酮干预组(给予生理剂量的睾酮补充),3个月后处死动物,取心脏,2剥离左心室,用半定量RT-PCR检测心肌组织中SERCA-2 a mRNA含量的变化。结果:睾酮干预组SERCA-2 a mRNA相对表达量较心衰组升高(0.516±0.075 vs 0.428±0.062,P<0.05),但依然低于假术手组(0.516±0.075 vs 0.572±0.063,P<0.05)。结论:睾酮可使心肌组织SERCA-2 amRNA含量上升,睾酮补充疗法可能是改善心衰的分子机制之一。
文摘目的:探讨睾酮改善心力衰竭(心衰)可能的分子生物学机制。方法:将SD大鼠随机分为假手术组、心衰组和心衰睾酮干预组(给予生理剂量的睾酮补充),后2组建立心衰模型,饲养观察3个月后处死动物,取心脏,剥离左心室,用半定量RT-PCR检测心肌组织中Fas、SERCA-2a mRNA含量的变化。结果:睾酮干预组FasmRNA相对表达量较心衰组显著降低(0.535±0.041 vs 0.570±0.060,P<0.05),但仍高于假手术组(0.431±0.056,P<0.05);睾酮干预组SERCA-2amRNA相对表达量较心衰组升高(0.516±0.075 vs 0.428±0.062P<0.05),但依然低于假术手组(0.572±0.063,P<0.05)。结论:睾酮可使心肌组织Fas含量下降、SERCA-2a mRNA含量上升,睾酮补充疗法可能是改善心衰的分子机制之一。
基金supported by the National Natural Science Foundation of China(81970202,81903609,U21A20339)the Natural Science Foundation of Heilongjiang Province,China(LH2022H002)+1 种基金the Outstanding Young Talent Research Fund of College of Pharmacy,Harbin Medical University(2019-JQ-02)2021(the second batch)Research Funds for affiliated research institutes in Heilongjiang Province(CZKYF2021-2-C013).
文摘Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.
