目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2...目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2020年2月~2021年6月在华北石油管理局总医院诊断为ACS的患者156例,包括不稳定型心绞痛(unstable angina,UA)80例(UA组)和急性心肌梗死(acute myocardial infarction,AMI)76例(AMI组);另选取同期体检健康者100例作为对照组。实时荧光定量PCR法检测受试者血清LncRNA XIST和miR-330-3p水平;24 h动态心电图检测受试者心率变异性(heart rate variability,HRV)时域指标[包括:24 h内正常R-R间期标准差(SDNN)、每5 min R-R间期平均值的标准差(SDANN)、每5 min R-R间期标准差的平均值(SDNN index)、相邻R-R间期之差的均方根(RMSSD)及相邻R-R间期相差>50 ms心搏数占总心搏数的百分比(PNN50)]以及Pearson法分析ACS患者血清LncRNA XIST和miR-330-3p水平与HRV时域指标的相关性。结果与对照组比较,UA组和AMI组血清LncRNA XIST(1.37±0.26,1.69±0.31 vs 1.09±0.22)水平升高(F=113.587,P=0.000),miR-330-3p(0.82±0.15,0.53±0.12 vs 1.03±0.18)及SDANN(115.96±19.57 ms,98.96±16.57 ms vs 133.43±21.01 ms),SDNN(113.84±15.26 ms,101.84±11.22 ms vs 136.41±31.53 ms),SDNN index(54.68±6.72 ms,46.73±5.14 ms vs 64.68±10.64 ms),RMSSD(27.48±5.62 ms,21.37±3.64 ms vs 36.48±8.62 ms)和PNN50(7.58%±2.83%,4.18%±1.13%vs 10.72%±3.21%)水平均降低(F=54.923~225.201,均P=0.000),差异均有统计学意义。与UA组比较,AMI组血清LncRNA XIST水平升高(t=10.792,P<0.05),miR-330-3p及SDANN,SDNN,SDNN index,RMSSD和PNN50水平降低,差异有统计学意义(t=4.743~16.538,均P<0.05);ACS患者血清LncRNA XIST与SDNN index,RMSSD和PNN50呈负相关(r=-0.465,-0.532,-0.542,均P<0.05);miR-330-3p与SDNN index,RMSSD和PNN50呈正相关(r=0.471,0.562,0.561,均P<0.05)。结论ACS患者血清LncRNA XIST水平升高,miR-330-3p水平降低,与心脏自主神经功能有关,可作为防治ACS的重要靶点。展开更多
Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's dis...Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.展开更多
文摘目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2020年2月~2021年6月在华北石油管理局总医院诊断为ACS的患者156例,包括不稳定型心绞痛(unstable angina,UA)80例(UA组)和急性心肌梗死(acute myocardial infarction,AMI)76例(AMI组);另选取同期体检健康者100例作为对照组。实时荧光定量PCR法检测受试者血清LncRNA XIST和miR-330-3p水平;24 h动态心电图检测受试者心率变异性(heart rate variability,HRV)时域指标[包括:24 h内正常R-R间期标准差(SDNN)、每5 min R-R间期平均值的标准差(SDANN)、每5 min R-R间期标准差的平均值(SDNN index)、相邻R-R间期之差的均方根(RMSSD)及相邻R-R间期相差>50 ms心搏数占总心搏数的百分比(PNN50)]以及Pearson法分析ACS患者血清LncRNA XIST和miR-330-3p水平与HRV时域指标的相关性。结果与对照组比较,UA组和AMI组血清LncRNA XIST(1.37±0.26,1.69±0.31 vs 1.09±0.22)水平升高(F=113.587,P=0.000),miR-330-3p(0.82±0.15,0.53±0.12 vs 1.03±0.18)及SDANN(115.96±19.57 ms,98.96±16.57 ms vs 133.43±21.01 ms),SDNN(113.84±15.26 ms,101.84±11.22 ms vs 136.41±31.53 ms),SDNN index(54.68±6.72 ms,46.73±5.14 ms vs 64.68±10.64 ms),RMSSD(27.48±5.62 ms,21.37±3.64 ms vs 36.48±8.62 ms)和PNN50(7.58%±2.83%,4.18%±1.13%vs 10.72%±3.21%)水平均降低(F=54.923~225.201,均P=0.000),差异均有统计学意义。与UA组比较,AMI组血清LncRNA XIST水平升高(t=10.792,P<0.05),miR-330-3p及SDANN,SDNN,SDNN index,RMSSD和PNN50水平降低,差异有统计学意义(t=4.743~16.538,均P<0.05);ACS患者血清LncRNA XIST与SDNN index,RMSSD和PNN50呈负相关(r=-0.465,-0.532,-0.542,均P<0.05);miR-330-3p与SDNN index,RMSSD和PNN50呈正相关(r=0.471,0.562,0.561,均P<0.05)。结论ACS患者血清LncRNA XIST水平升高,miR-330-3p水平降低,与心脏自主神经功能有关,可作为防治ACS的重要靶点。
基金supported by the National Institute on Aging (NIA)National Institutes of Health (NIH)+3 种基金Nos.K99AG065645,R00AG065645R00AG065645-04S1 (to SK)NIH research grants,NINDS,No.R01 NS115834NINDS/NIA,No.R01 NS115834-02S1 (to LG)。
文摘Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.
