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Neural Regeneration Research 2019年第6期14卷 954-961页

作者： Ya-Guang Huang Wei Tao Song-Bai Yang Jin-Feng Wang Zhi-Gang Mei Zhi-Tao Feng Medical College of China Three Gorges University Yichang Hospital of Traditional Chinese Medicine Clinical Medical College of Traditional Chinese MedicineChina Three Gorges University

Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling *** review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.

关键词： nerve regeneration autophagy electroacupuncture cerebral ischemia/reperfusion injury mTOR LC3 Beclin1 p62 neuroprotection neural regeneration

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury

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Neural Regeneration Research 2020年第3期15卷 548-556页

作者： Si-Qun Jing Sai-Sai Wang Rui-Min Zhong Jun-Yan Zhang Jin-Zi Wu Yi-Xian Tu Yan Pu Liang-Jun Yan Yingdong College of Food Science and Engineering Shaoguan UniversityShaoguanGuangdong ProvinceChina School of Bioengineering Jiangnan UniversityWuxiJiangsu ProvinceChina Department of Pharmaceutical Sciences UNT System College of PharmacyUniversity of North Texas Health Science CenterFort WorthTXUSA College of Life Sciences and Technology Xinjiang UniversityUrumqiXinjiang Uygur Autonomous RegionChina

Orientin is a flavonoid *** recent years,its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia,anti-apoptosis,anti-radiation,anti-tumor,and ***,the neuroprotective effects of Orientin on stroke injury have not been comprehensively *** aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus ***(CLO)from Cyperus esculentus *** against ischemia/reperfusion(I/R)injury using standard orientin as *** in vitro studies,we treated HT22 cells with CoCl2 as an in vitro ischemic injury ***22 cells in the control group were treated with *** in vivo studies,we used rat models of middle cerebral artery occlusion,and animals that received sham surgery were used as *** found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein ***,CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide *** showed that CLO could decrease neurological deficit score,attenuate brain water content,and reduce cerebral infarct volume,leading to neuroprotection during cerebral ischemia-reperfusion *** studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical *** molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of *** experimental procedures and protocols were approved on May 16,2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China(approval ***20160516-57).

关键词： antioxidants caspase-3 cerebral ischemia/reperfusion injury cobalt chloride Cyperus esculentus L.orientin(CLO) lipid peroxidation nerve regeneration neurological deficits oxidative stress reactive oxygen species

Natural Products Improve Organ Microcirculation Dysfunction Following ischemia/reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

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Engineering 2024年第7期38卷 77-99页

作者： Jingyan Han Quan Li Kai Sun Chunshui Pan Jian Liu Ping Huang Juan Feng Yanchen Liu Gerald A.Meininger Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China Tasly Microcirculation Research Center Peking University Health Science CenterBeijing 100191China Key Laboratory of Stasis and Phlegm State Administration of Traditional Chinese Medicine of the People’s Republic of ChinaBeijing 100191China Beijing Laboratory of Integrative Microangiopathy Peking University Health Science CenterBeijing 100191China Dalton Cardiovascular Research Center and Department of Medical Pharmacology and Physiology University of MissouriColumbiaMO 65211USA

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and *** disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and *** clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory *** products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory *** recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international *** 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,*** review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue *** on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

关键词： ischemia/reperfusion Lipopolysaccharide Natural products Leukocyte activation Hyperpermeability

GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2019年第7期14卷 1221-1229页

作者： Zi-Wei Han Yue-Chen Chang Ying Zhou Hang Zhang Long Chen Yang Zhang Jun-Qiang Si Li Li Department of Physiology Medical College of Shihezi University Key Laboratory of Xinjiang Endemic and Ethnic Disease Shihezi University School of Medicine Affiliated Teng Zhou Central People's Hospital Jining Medical University Department of Physiology Jiaxing College of Medicine

Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) *** this study,three key proteins in the endoplasmic reticulum stress pathway(glucose-regulated protein 78,caspase-12,and C/EBP homologous protein) were selected to examine the potential mechanism of endoplasmic reticulum stress in the neuroprotective effect of G protein-coupled estrogen *** Sprague-Dawley rats received ovariectomy(OVX),and then cerebral I/R rat models(OVX+ I/R) were established by middle cerebral artery *** after I/R,rat models were injected with 100 μg/kg E2(OVX + I/R +E2),or 100 μg/kg G protein-coupled estrogen receptor agonist G1(OVX + I/R + G1) in the lateral *** scoring was used to detect neurobehavioral changes in each *** volumes were measured by 2,3,5-triphenyltetrazolium chloride *** changes in neurons were observed by Nissl *** dexynucleotidyl transferase-mediated nick end-labeling staining revealed that compared with the OVX + I/R group,neurological function was remarkably improved,infarct volume was reduced,number of normal Nissl bodies was dramatically increased,and number of apoptotic neurons in the hippocampus was decreased after E2 and G1 *** detect the expression and distribution of endoplasmic reticulum stress-related proteins in the endoplasmic reticulum,caspase-12 distribution and expression were detected by immunofluorescence,and mRNA and protein levels of glucose-regulated protein 78,caspase-12,and C/EBP homologous protein were determined by polymerase chain reaction and western blot *** results showed that compared with the OVX+ I/R group,E2 and G1 treatment obviously decreased mRNA and protein expression levels of glucose-regulated protein 78,C/EBP homologous protein,and ***,the G protein-coupled estrogen receptor antagonist G15(OVX + I/R + E2 + G15) could eli

关键词： nerve regeneration cerebral ischemia/reperfusion injury estrogen G protein-coupled estrogen receptor G1 G15 endoplasmic reticulum stress glucose-regulated protein 78 caspase-12 C/EBP homologous protein neuronal apoptosis neural regeneration

PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

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Neural Regeneration Research 2023年第2期18卷 357-363页

作者： Wei-Tao Yan Wen-Juan Zhao Xi-Min Hu Xiao-Xia Ban Wen-Ya Ning Hao Wan Qi Zhang Kun Xiong Department of Human Anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Human Resources Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina Key Laboratory of Emergency and Trauma Ministry of EducationCollege of Emergency and TraumaHainan Medical UniversityHaikouHainan ProvinceChina

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory *** our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of *** this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion *** results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in ***/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the *** results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

关键词： apoptosis gasdermin-D(GSDMD) ischemia/reperfusion mixed lineage kinase domain-like protein(MLKL) necroptosis NOD-like receptor protein 3(NLRP3) PANoptosis pyroptosis receptor-interacting protein kinase 3(RIPK3) retinal neuron

DNA hypomethylation promotes learning and memory recovery in a rat model of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2023年第4期18卷 863-868页

作者： Guang Shi Juan Feng Ling-Yan Jian Xin-Yu Fan Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Neurology The People’s Hospital of Liaoning ProvinceShenyangLiaoning ProvinceChina Department of Pharmacy Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Cerebral ischemia/reperfusion injury impairs learning and memory in *** have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and *** investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA *** results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion *** effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion *** findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion *** results provide theoretical evidence for stroke treatment using epigenetic methods.

关键词： cognitive memory DNA methylation DNMT1 hippocampus ischemia/reperfusion social memory spatial memory TET1 transient middle cerebral artery occlusion 5-aza-2′-deoxycytidine

Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

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Acta Pharmaceutica Sinica B 2015年第1期5卷 8-24页

作者： Kai Sun Jingyu Fan Jingyan Han Tasly Microcirculation Research Center Peking University Health Science Center Department of Integration of Chinese and Western Medicine School of Basic Medical Sciences Peking University Key Laboratory of Microcirculation State Administration of Traditional Chinese Medicine Key Laboratory of Stasis and Phlegm of State Administration of Traditional Chinese Medicine Beijing Institute of Integration of Chinese and Western Medicine for Microangiopathy

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound Tem preparation, Chinese materia medica, and active components on I/R-induced cerebral imicrocirculatory disturbances, brain injury and neuron damage. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. Alt rights reserved.

关键词： ischemia/reperfusion Antioxidant Leukocyte adhesion Hpyerpermeability Brain blood barrier Neuron

ESE1 expression correlates with neuronal apoptosis in the hippocampus after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2019年第5期14卷 841-849页

作者： Hai-Long Yu Liang-Zhu Wang Ling-Ling Zhang Bei-Lei Chen Hui-Juan Zhang Yu-Ping Li Guo-Dong Xiao Ying-Zhu Chen Clinical Medical College of Yangzhou University Department of Neurology Northern Jiangsu People's Hospital Institute of Neuroscience Northern Jiangsu People's Hospital Drum Tower Hospital Medical School of Nanjing University Dalian Medical University Department of Neurology Second Affiliated Hospital of Soochow University

Epithelial-specific ETS-1(ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride(CoCl_2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl_2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl_2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.

关键词： stroke epithelial specific ETS-1 cerebral ischemia/reperfusion nuclear factor-κB inflammation caspase-3 neuroprotective effects neural regeneration cobalt chloride(CoCl2) siRNA transfection

Insulin improves cardiomyocyte contractile function through enhancement of SERCA2a activity in simulated ischemia/reperfusion

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Acta Pharmacologica Sinica 2006年第7期27卷 919-926页

作者： Jie YU~2 Hai-feng ZHANG~2 Feng WU~2 Qiu-xia LI~2 Heng MA~2 Wen-yi GUO~3 Hai-chang WANG~3 Feng GAO~(2,3,4,5)2 Department of Physiology3 Department of Cardiology,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China 4 Institute of Molecular Medicine,Peking University,Beijing 100871,China Department of Physiology Xijing Hospital Fourth Military Medical University Xi'an China Department of Cardiology Xijing Hospital Fourth Military Medical University Xi'an China Institute of Molecular Medicine Peking University Beijing China

Aim:Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronaryendothelial cells following ischemia/reperfusion（I/R）via the Akt-endothelial ni-tric oxide synthase survival signal *** important insulin signalingmight further contribute to the improvement of cardiac function after *** this study,we tested the hypothesis that sarcoplasmic reticulum calcium-AT-Pase（SERCA2a）is involved in the insulin-induced improvement of cardiac con-tractile function following I/***:Ventricular myocytes were enzymaticallyisolated from adult SD *** I/R was induced by perfusing cells withchemical anoxic solution for 15 min followed by reperfusion with Tyrode's solu-tion with or without insulin for 30 *** shortening and intracellularcalcium transients were assessed and underlying mechanisms were ***:reperfusion with insulin(10-7mol/L)significantly improved the recoveryof contractile function（n=15-20 myocytes from 6-8 hearts,P<0.05）,and increasedcalcium transients,as evidenced by the increased calcium(Ca2+)fluorescenceratio,shortened time to peak Ca2+and time to 50% diastolic Ca2+,compared withthose in cells reperfused with vehicle（P<0.05）.In addition,Akt phosphorylationand SERCA2a activity were both increased in insulin-treated I/R cardiomyocytes,which were markedly inhibited by pretreatment of cells with a specific Akt ***,inhibition of Akt activity abolished insulin-induced positive contrac-tile and calcium transients responses in I/R ***:Thesedata demonstrated for the first time that insulin improves the recovery of contrac-tile function in simulated I/R cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion.

关键词： insulin ischemia/reperfusion cardiomyocyte contraction calcium transients SERCA2a Akt

Electroacupuncture treatment improves motor function and neurological outcomes after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2022年第7期17卷 1545-1555页

作者： Si-Si Li Xu-Yun Hua Mou-Xiong Zheng Jia-Jia Wu Zhen-Zhen Ma Xiang-Xin Xing Jie Ma Chun-Lei Shan Jian-Guang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Center of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina

Electroacupuncture(EA)has been widely used for functional restoration after ***,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly *** this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and *** found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and ***,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic *** kinase B inhibitor ANA-12 weakened the therapeutic effects of *** findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal *** procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval ***200110002)on January 10,2020.

关键词： brain-derived neurotrophic factor dendritic electroacupuncture ischemia/reperfusion motor function neurite outgrowth inhibitor-A neurological outcomes Nogo receptor synapse tyrosine kinase B