Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important...Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.展开更多
目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好...目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。展开更多
基金supported by the Science and Technology Development Plan Project of Jilin Province,No.YDZJ202401157ZYTS(to SL).
文摘Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.
文摘目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。
