The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
文摘目的探讨胃癌组织中EB病毒的感染状况,分析其与小核核糖核蛋白多肽A(Small nuclear ribonucleoprotein polypeptide A,SNRPA)及端粒沉默破坏因子1样蛋白(Disruptor of telomeric silencing 1-like,DOT1L)表达的相关性。方法收集2022年2月至2025年5月南阳市第一人民医院收治的280例胃癌患者的癌组织及癌旁正常组织标本。分析EB病毒感染与患者临床病理特征的关系,比较EB病毒感染阳性组与阴性组中SNRPA、DOT1L的表达水平,采用Spearman分析EB病毒感染与癌组织SNRPA、DOT1L表达的相关性,受试者工作(Receiver operating characteristic,ROC)曲线分析SNRPA、DOT1L对胃癌EB病毒感染的诊断价值。结果280例胃癌患者癌组织标本中EB病毒阳性者33例,阳性率11.79%(33/280);胃癌患者EB病毒感染与淋巴结转移相关(P<0.05);SNRPA与DOT1L在胃癌组织中的表达均高于癌旁组织,EB病毒感染组SNRPA与DOT1L的表达均高于EB病毒未感染组(P<0.05);Spearman相关性分析显示,癌组织SNRPA、DOT1L表达与EB病毒感染呈正相关(r=0.709、0.658,P<0.05)。ROC曲线显示,SNRPA、DOT1L、两种指标联合评估胃癌EB病毒感染的曲线下面积(Area Under the Curve,AUC)分别为0.807、0.773、0.886。结论EB病毒感染与胃癌患者淋巴结转移、SNRPA、DOT1L表达水平有关,联合检测SNRPA、DOT1L可提高胃癌EB病毒感染的诊断效能。
