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TIR-domain-containing adapter-inducing interferon-βdeficiency promote retinal ganglion cell survival and axon regeneration by microglial inactivation

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TIR-domain-containing adapter-inducing interferon-βdeficien...

Association and linkage analysis of COLIA1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Sen LIN~(1,2),Ya-Jie LIANG~2,Qiang GUO~2,Hong-Li ZHOU~1,Ji-Qiang ZHANG~2,Chen BIAN~2,Can WEN~2,Yan-Ling ZHANG~2,Ying XIONG~2,Shu-Rong LI~(1,3,*),Bing-Yin su~(1,*) 1 Development and Regeneration Key Laboratory of Sichuan Province,Department of Histo-embryology and Neurobiology,Chengdu Medical College,Chengdu 610083,China 2 Department of Neurobiology,Third Military Medical University,Chongqing 400038,China 3 Department of Pathology,Chengdu Medical College,Chengdu 610083,China

TIR-domain-containing adapter-inducing interferon-β(TRIF) is a downstream adaptor of Toll-like receptor(TLR) 4 which is one of the major signal pathways in immune cells leading to neuroinflammtion in central nervous *** present study was to elucidate the effect of TRIF deficiency on optic nerve(ON) regeneration and retinal ganglion cell(RGC) survival in ON crush model,by means of immunoflurosence,fluro-gold retrograde label,co-culture and real-time PCR(polymerase chain reaction).Using TRIF knock-out(ko) mice,however,no significant regeneration was found in RGC *** survival ratio of RGCs was remarkably higher in TRIF ko group when compared with wild type(WT) group in the crush *** immunostained microglia and found that optic nerve lesion induced more microglial activation in WT group(409±34,per retina) than TRIF"’" group(234±28,per retina).Also in a transwell co-cultured system,WT microglia migrated through the transwell *** contrast,few TRIF microglia did so when performed in in vitro crush model on *** immediate consequence of inactivation of microglia is reduced production of cytokines like interferon-β(IFN-β).This is supported by our finding that the relative mRNA expression of IFN-βin TRIF group was decreased about 50%than that in WT group and the degenerated function of IFN-βwas reduced by IFN-βantibody in a transwell co-culture ***,our results indicated that TRIF deficiency promotes axon regeneration in ON via attenuation of microglia activation and consequent reduction in release of harmful cytokines,especially IFN-β.

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Acta Pharmacologica Sinica 2007年第3期 375-381页

作者： Hui JIANG~(2,3,5) Shu-feng LEI~(2,5) su-mei XIAO~2 Yuan CHEN~(2,3) Xiao suN~2 Fang YANG~(2,3) Li-ming LI~2 Shan WU~2 Hong-wen DENG~(2,4,6)2 Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education,College of Life Sciences,Hu-nan Normal University,Changsha 410081,China 3 Osteoporosis Research Center,Creighton University,Omaha 68131,USA 4 Department of Orthopedic surgery,School of Medicine,University of Missouri-Kansas City,Kansas City 64108,USA

Aim:To simultaneously investigate the contribution of the alpha 1 chain of col-lagen type 1(COLlAl)and alpha2-HS-glycoprotein(AHSG)genes to the varia-tion of bone geometric parameters in both Caucasians and ***:Sixhundred and five Caucasian individuals from 157 nuclear families and 1228 Chi-nese subjects from 400 nuclear families were genotyped at the AHSG-Sacl,COLIA1-PCOL2 and Spl polymorphisms using polymerase chain reaction(PCR)-restric-tion fragment length polymorphism(RFLP).5 FN bone geometric parameters werecalculated based on bone mineral density and bone area of femoral neck(FN)measured by dual energy X-ray *** stratification,totalfamily association,within-family association,and linkage tests were performed bythe quantitative transmission disequilibrium test ***:The t-testshowed the significant differences of all bone geometric phenotypes(except ED)between Caucasians and Chinese in the offspring using both unadjusted andadjusted(by age,height,weight,and gender)*** Caucasians,we foundsignificant within-family association results between the COLlAl-Spl polymor-phism(rs1800012)and cross sectional area(CSA),cortical thickness(CT),endocortical diameter(ED),buckling ratio(BR)(P=0.018,0.002,0.023,and 0.001,respectively);the COLlAl-Spl polymorphism also detected significant linkagewith BR(P=0.039).In the population of China,the within-family associationsbetween the COLlAl-PCOL2 polymorphism(rs1107946)and CT,BR were signifi-cant(P=0.012 and 0.008,respectively).Furthermore,evidence of linkage wereobserved between the AHSG-Sacl polymorphism(rs4918)and CT,BR(P=0.042and 0.014,respectively)in Caucasians,but not in ***:Ourresults suggest that the COLlAl gene may have significantly association withbone geometry in both Caucasians and Chinese,and the AHSG gene may belinked to bone geometry in Caucasians,but not in *** study representsour first efforts on investigating the importance of the COLlAl and A

关键词： COLIA1 AHSG bone geometry transmission disequilibrium test

表面肌电联合等速肌力测试仪在膝骨性关节炎患者功能评估中的应用

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按摩与康复医学 2020年第2期11卷 30-32页

作者：梁杰卢惠苹陈述荣苏婵娟张高飞卢萍丹陈婧姈陈昕福州市第二医院福建中医药大学

目的:探讨表面肌电图联合等速肌力测试仪在精准评估膝骨性关节炎(koA)患者膝关节肌肉功能、运动能力和稳定性的应用。方法:采用表面肌电图联合等速肌力测试仪定量评估25例koA和25例健康者膝关节肌肉功能、运动能力和稳定性,并统计分析... 详细信息

目的:探讨表面肌电图联合等速肌力测试仪在精准评估膝骨性关节炎(koA)患者膝关节肌肉功能、运动能力和稳定性的应用。方法:采用表面肌电图联合等速肌力测试仪定量评估25例koA和25例健康者膝关节肌肉功能、运动能力和稳定性,并统计分析比较。结果:在角速度为60°/s的等速向心测试时koA组患侧膝关节股四头肌和胭绳肌平均肌电值、平均功率频率斜率,峰力矩、总做功量明显低于健康组(PkoA患者膝关节功能的重要检测手段。

关键词：膝骨性关节炎表面肌电等速肌力平衡

心肌特异性Creg基因条件敲除小鼠的建立及表型分析

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现代生物医学进展 2016年第36期16卷 7001-7005,7010页

作者：田孝祥刘丹刘美丽刘艳霞齐艳萍吴鹏苏慧敏闫承慧韩雅玲沈阳军区总医院心血管病研究所心内科辽宁沈阳110016 南京大学模式动物研究中心江苏南京210089

目的:建立心肌特异性Creg基因敲除小鼠并初步分析其表型。方法:利用订购的Creg两端插入lox P位点(Cregflox/flox)的小鼠与肌型肌酸激酶特异性启动子驱动的Cre重组酶转基因(Ckmm-cre)小鼠交配,获得Cregflox/+/Ckmm-cre小鼠。再利用Cregfl... 详细信息

目的:建立心肌特异性Creg基因敲除小鼠并初步分析其表型。方法:利用订购的Creg两端插入lox P位点(Cregflox/flox)的小鼠与肌型肌酸激酶特异性启动子驱动的Cre重组酶转基因(Ckmm-cre)小鼠交配,获得Cregflox/+/Ckmm-cre小鼠。再利用Cregflox/+/Ckmm-cre小鼠互相交配,获得基因型为Cregflox/flox/Ckmm-cre的心肌特异性Creg基因条件敲除(Creg conditional knockout,Creg c ko)小鼠。用PCR法进行基因型鉴定。用定量PCR及Western Blot检测心肌组织中Creg表达水平。HE染色观察敲除小鼠与同窝野生型对照小鼠心脏大小及形态。检测两组小鼠心电图。用小动物超声评价两组小鼠左心室收缩功能。结果:1经基因型鉴定,成功获得Creg c ko小鼠。2与野生型对照相比,Creg c ko小鼠心脏中CREG在转录及翻译水平表达降低90%以上。3与野生型对照相比,Cre c ko小鼠的心脏大小、形态、心电图及左心室射血分数均无显著差别。结论:成功建立心肌特异性CREG基因条件敲除小鼠,为进一步研究Creg在心脏疾病中的作用和机制提供了有力的工具。

关键词： Creg 条件敲除心肌细胞表型

牛痘相关激酶2在神经发育过程中小胶质细胞介导的突触消除中起重要作用

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神经损伤与功能重建 2019年第5期14卷 F0003-F0003页

作者： Lee J Lee S Ryu YJ Lee D Kim S Seo JY Oh E Paek SH Kim su Ha CM Choi SY Kim KT 聂昊(编译) Division of Integrative Biosciences and Biotechnology Pohang University of Science and Technology Pohang Republic of Korea Department of Physiology Dental Research Institute Seoul National University School of Dentistry Seoul Republic of Korea Research Division and Brain Research Core Facilities of korea Brain Research Institute Daegu Republic of Korea Department of Life Sciences Pohang University of Science and Technology Pohang Republic of Korea Neuroregeneration and Stem Cell Programs Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore Maryland Department of Neurosurgery Seoul National University College of Medicine Seoul South Korea University of British Columbia Vancouver British Columbia Canada 不详

在出生后的神经发育过程中,大脑神经回路的建立需要小胶质细胞消除过度的突触连接。小胶质细胞突触调节缺失已被证实与自闭症、精神分裂症和智力残疾等神经发育障碍有关。小胶质细胞中表达的牛痘相关激酶2(VRK2)可能可以激活突触消除的... 详细信息

在出生后的神经发育过程中,大脑神经回路的建立需要小胶质细胞消除过度的突触连接。小胶质细胞突触调节缺失已被证实与自闭症、精神分裂症和智力残疾等神经发育障碍有关。小胶质细胞中表达的牛痘相关激酶2(VRK2)可能可以激活突触消除的过程。在VRK2缺陷小鼠(VRK2ko)中,可以观察到小胶质细胞内突触前位点的减少。而且,在出生后第2周,VRK2ko小鼠的突触前位点和突出的数量都出现了异常增加。这些差异并没有持续到成年期。尽管突触数量的增加最终结局与正常小鼠无异,但成年VRK2ko小鼠在社交行为、情境恐惧记忆和空间记忆中表现出行为缺陷。

关键词：牛痘相关激酶2 小胶质细胞神经发育突触消除

IL-17在黏附侵袭性大肠杆菌感染小鼠结肠过程中的作用机制研究

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现代生物医学进展 2017年第17期17卷 3211-3215,3205页

作者：张海佳沙素梅徐斌王虎许冰王国栋蒋铭佐聂勇战吴开春李孟彬第四军医大学西京消化病医院陕西西安710032 中国人民解放军第174医院福建厦门361000

目的:评价IL-17在黏附侵袭性大肠杆菌感染小鼠结肠过程中的作用及其可能机制。方法:选择野生型及IL-17基因敲除的SPF级C57BL/6小鼠并随机分成4组,分别给予不同的处理:(1)野生小鼠+单纯蒸馏水灌胃处理组;(2)野生小鼠+*** LF82(1×109/CFU... 详细信息

目的:评价IL-17在黏附侵袭性大肠杆菌感染小鼠结肠过程中的作用及其可能机制。方法:选择野生型及IL-17基因敲除的SPF级C57BL/6小鼠并随机分成4组,分别给予不同的处理:(1)野生小鼠+单纯蒸馏水灌胃处理组;(2)野生小鼠+*** LF82(1×109/CFU/只)灌胃10天处理组;(3)IL-17敲除小鼠+单纯蒸馏水灌胃处理组;(4)IL-17敲除小鼠+*** LF82灌胃10天处理组。从以下5个方面评价各组小鼠的炎症反应和IL-17水平:(1)组织病理评分评估炎症反应严重程度;(2)透射电镜下观察结肠上皮细胞的超微结构;(3)免疫组织化学检测结肠分泌的IL-17;(4)PCR检测小鼠结肠中IL-17m RNA表达;(5)ELISA检测结肠组织中IL-17的含量。结果:定植了*** LF82的IL-17敲除小鼠肠道炎症程度和超微结构损伤较野生型小鼠更加严重(P<0.05)。与未经*** LF82处理组相比,定植了*** LF82的野生小鼠肠道中IL-17m RNA和IL-17含量明显升高(P<0.05)。结论:IL-17在*** LF82在黏附侵袭结肠粘膜过程中的保护作用,IL-17是针对AIEC菌株*** LF82免疫的重要效应物,而结肠局部分泌增加的IL-17会改善感染的结果。

关键词：炎症性肠病大肠杆菌LF82 白细胞介素17

TLR4-Nrf2/HO-1信号通路在小鼠机械通气所致肺损伤的作用研究

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现代生物医学进展 2018年第20期18卷 3812-3816页

作者：李艳艳潘频华苏晓丽胡成平刘帅李海涛黎皓思李毅戴敏慧毛志李千中南大学湘雅医院呼吸危重症医学科湖南长沙410008

目的:机械通气作为一重要措施,拯救呼吸衰竭患者的生命,有致肺血管炎症及渗透增加等病变的可能,即VILI。本研究旨在明确VILI是否受潮气量、Toll样受体4(Toll-like receptor-4,TLR4)基因敲除及核因子-E2相关受体2/血红素氧化酶-1(Nuclear... 详细信息

目的:机械通气作为一重要措施,拯救呼吸衰竭患者的生命,有致肺血管炎症及渗透增加等病变的可能,即VILI。本研究旨在明确VILI是否受潮气量、Toll样受体4(Toll-like receptor-4,TLR4)基因敲除及核因子-E2相关受体2/血红素氧化酶-1(Nuclear factor-erythroid 2 related factor2/heme oxygenase 1,Nrf2/HO-1)表达的激活关联是否存在。方法:TLR4基因缺失和野生型(WT)小鼠分别分为对照(CON),低潮气量(low tidal volume,LTV)和高潮气量(high tidal volume,HTV)组。给小鼠禁食、禁水12小时后,麻醉小鼠,做气管切开,将气管导管经口插入,通气4小时,呼气末正压(PEEP)2 cm H2O,R:100次/分钟,吸呼比1:2;CON组仅气管插管。小鼠处死,测湿/干重比(W/D)。肺组织依次:HE染色组织学评价;评价肺损伤评分;测定肺炎症因子表达:肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及白介素-1β(interleukin-1β,IL-1β);免疫组化及免疫印迹法,测Nrf2蛋白值;测HO-1蛋白值。结果:在WT+HTV组,Nrf2和HO-1的表达比较WT+LTV组明显升高,但受到TLR4基因敲除的调节,相应的TLR4基因敲除组升高更明显。肺损伤评分、湿/干比在WT+HTV组增加,相应的TLR4基因敲除组升高更显著。结论:HTV通气可致小鼠VILI。VILI小鼠肺中的Nrf2/HO-1表达升高,TLR4基因缺失可以升高Nrf2/HO-1表达,保护肺组织,减轻VILI。

关键词： Toll样受体4 核因子-E2相关受体2 血红素氧化酶-1 机械通气相关肺损伤