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In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & vascular neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan Xia Meng Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina National center for neurological Diseases BeijingChina Advanced Innovation center for Human Brain protection Capital Medical UniversityBeijingChina China National Clinical research center for neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry *** estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were *** analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were *** Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were *** adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild *** with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild *** analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year *** BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 ***,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

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Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & vascular neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research center for neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina National center for neurological Diseases BeijingChina Advanced Innovation center for Human Brain protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment ***,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic ***,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains *** To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin *** Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in *** patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to *** primary endpoint is a new stroke or END within 90 *** primary safety endpoint is severe or moderate bleeding within 90 *** The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with *** registration number NCT05310968.

关键词： Aspirin regimen centre

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Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

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Journal of Environmental Sciences 2024年第5期139卷 460-472页

作者： Sujie Sun Li Zhang Xue Li Lu Zang Ling Huang Junquan Zeng Zigang Cao Xinjun Liao Zilin Zhong Huiqiang Lu Jianjun Chen Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of OrgansCenter for Clinical Research Center of the Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Translational research Institute of Brain and Brain-like Intelligence Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationDepartment of PediatricsShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China State Environmental protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants School of Environmental Sciences and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Interventional and vascular Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Department of Internal Medicine and Hematology Affiliated Hospital of Jinggangshan UniversityJi’an 343009China

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water ***,little is known regarding its toxic effects on cardiovascular ***,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L *** showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart ***,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart *** sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic ***-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular ***-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism ***-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting ***,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

关键词： Hexafluoropropylene oxide trimer acid Heart development vascular development Hemopoiesis Zebrafish embryos

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Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease

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Science China Life Sciences 2024年

作者： Wen-Tao Sun Jian-Yong Du Jia Wang Yi-Long Wang Er-Dan Dong research center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital)School of Health and Life SciencesUniversity of Health and Rehabilitation Sciences Department of Cardiology and Institute of vascular Medicine Peking University Third HospitalThe Institute of Cardiovascular SciencesPeking UniversityState Key Laboratory of Vascular Homeostasis and RemodelingPeking University

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells(EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro-and microvasculature.

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“Standby” EMT and “immune cell trapping” structure as novel mechanisms for limiting neuronal damage after CNS injury

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Neural Regeneration research 2014年第23期9卷 2032-2035页

作者： Jong-Ho Cha Kyu-Won Kim snu-harvard neuro vascular protection research center College of Pharmacy Seoul National University Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and Technology and College of Medicine or College of PharmacySeoul National University

The central nervous system （CNS） contains the two most important organs, the brain and spinal cord, for the orchestration of the mental and physical activities of life. Because of its importance, the human body has evolved barrier systems to protect CNS tissue from the external environment. This barrier is a membrane composed of tightly apposed cells and is selectively permeable to specific molecules by way of membrane transporters.

关键词： EMT and immune cell trapping Standby CNS structure as novel mechanisms for limiting neuronal damage after CNS injury cell

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Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

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Stroke & vascular neurology 2024年第1期9卷 66-74页

作者： Xuan Sun Ming Yang Dapeng Sun Guangge Peng Yiming Deng Xingquan Zhao Liping Liu Ning Ma Feng Gao Dapeng Mo Wengui Yu Yongjun Wang Yilong Wang Zhongrong Miao Department of Interventional neuroradiology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of neurology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of neurology Comprehensive Stroke&Cerebrovascular CenterUniversity of California IrvineIrvineCaliforniaUSA Chinese Institute for Brain research BeijingChina National center for neurological Diseases BeijingChina Advanced Innovation center for Human Brain protection Capital Medical UniversityBeijingChina China National Clinical research center for neurological Diseases BeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for *** Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with *** eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial *** eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 *** groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style *** participants will be followed up for *** outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary *** BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating *** registration number NCT03703635;https://***.

关键词： balloon prospective centre

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK center for Life Nano-and neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation center for Human Brain protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

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Neural Regeneration research 2024年第7期19卷 1618-1624页

作者： Luyi Wang Man Xu Yan Wang Feifei Wang Jing Deng Xiaoya Wang Yu Zhao Ailing Liao Feng Yang Shali Wang Yingbo Li Institute of neuroscience Department of PhysiologySchool of Basic Medical ScienceChongqing Medical UniversityChongqingChina Department of Pediatric Chongqing University Fuling HospitalChongqingChina Department of neurosurgery Xinqiao HospitalArmy Medical UniversityChongqingChina Department of Pathology Affiliated Hospital of North Sichuan Medical CollegeNanchongSichuan ProvinceChina NHC Key Laboratory of Birth Defects and Reproductive Health Chongqing Population and Family Planning Science and Technology Research InstituteChongqingChina China National Clinical research center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Advanced Innovation center for Human Brain protection Capital Medical UniversityBeijingChina

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate ***2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic *** role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea *** the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal *** findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout ***,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this *** pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic *** findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

关键词： autism Ctnnd2 deletion GABAergic neurons melatonin PI3K/Akt signal pathway prefrontal cortex social behavior spine density synaptic-associated proteins

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Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1599-1605页

作者： Yan-Xia Wu Shuo Yin Shan-Shan Song Xiang Liu Yu-Xuan Deng Xue-Jing Lu Eye School of Chengdu University of Traditional Chinese Medicine Chengdu 610075Sichuan ProvinceChina Ineye Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610084Sichuan ProvinceChina School of Chinese Classics Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina Key Laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function protection with Traditional Chinese Medicine Chengdu 610075Sichuan ProvinceChina Retinal Image Technology and Chronic vascular Disease Prevention&Control and Collaborative Innovation center Chengdu 610075Sichuan ProvinceChina

AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in ***:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for *** 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were ***:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model ***-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model ***-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the ***:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.

关键词： retinal ischemia-reperfusion Lycium barbarum glycopeptide pretreatment anti-inflammatory antioxidative rat

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