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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptorinduced cardiomyocyte hypertrophy

Acta Pharmacologica Sinica 2006年第7期27卷 895-900页

作者： Da-li LUO~(2,3.5) Jian GAO~2 Xiao-mei LAN~3.Gang WANG~4 Sheng WEI~4 Rui-ping XIAO~4 Qi-de HAN~3. Department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of Medical sciences,Beijing 100069,{3. 3.institute of cardiovascular science at health science center,peking university Beijing 100083.china 4 institute of Molecular Medicine and College of Life science,peking university,Beijing 100871,{3. Department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing 100069 China institute of cardiovascular science at {3. science center Peking University Beijing 100083 China institute of Molecular Medicine and College of Life science Peking University Beijing 100871 China

Aim:Intracellular Ca2+plays pivotal roles in diverse cellular functions,includinggene transcription that underlies cardiac remodeling during stress ***,the role of inositol 1,4,5-trisphosphate receptors（IP3.s）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3.smay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3.s was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3.M）,a membrane-permeant ester of IP3.to activate IP3.s directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3.M(10μmol·L-1)mimicked theeffects of phenylephrine,a selective agonist of α1AR,in increments in local Ca2+spark release（especially in the perinuclear area）and global Ca2+*** importantly,IP3. inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3.M-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3.]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3. signaling to α1AR-stimulatedgene expression and cardiomyocyte hypertrophy.

关键词： inositol 1,4,5-trisphosphate receptors Ca2+sparks α1 adrenergic stimulation cardiac hypertrophy

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Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3.plus nicotine in rats

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Acta Pharmacologica Sinica 2006年第3期27卷 299-306页

作者： Sheng-ying WU~(2,6) Chun-shui PAN~3.Bin GENG~3.Jing ZHAO~3.Fang YU~3.Yong-zheng PANG~3.Chao-shu TANG~4 Yong-fen QI~(3.4,5) ~2institute of cardiovascular Disease,peking {3. First Hospital.Beijing 10003. ~3.epartment of Physiology and Pathophysiology,peking {3. health science center,Beijing 100083.china,~4Key Laboratory of Molecular cardiovascular science,Ministry of Education,Beijing 100083.china 2institute of cardiovascular Disease Peking University First Hospital Beijing 100034 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 3.epartment of Physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China 4Key Laboratory of Molecular cardiovascular science Ministry of Education Beijing 100083 China 4Key Laboratory of Molecular cardiovascular science Ministry of Education Beijing 100083 China

Aim:To investigate the role of the endogenous cystathionine γ-synthase(CSE)/hydrogen sulfide(H2S)pathway in vascular calcification in ***:A ratvascular calcification model was established by administration of vitamin D3.plusnicotine(VDN).The amount of CSE and osteopontin(OPN)mRNA was deter-mined by using semi-quantitative reverse-transcription polymerase chain *** calcium content,45Ca2+accumulation and alkaline phosphatase(ALP)activitywere measured.H,S production and CSE activity were ***:yonKossa staining produced strong positive black/brown staining in areas amongthe elastic fibers of the medial layer in the calcified *** calcium content,45Ca2+accumulation and ALP activity in calcified arteries increased by 6.77-,1.42-,and 1.87-fold,respectively,compared with *** expression of the OPNgene was upregulated(P3..8%,40.75% and 63.5% lowerin the low-dosage NariS group than in the VDN group,respectively(P3.9%,3..8 % and 46.2% lower in the aorta in the high-dosage NariS group than in theVDN group,respectively(P<0.01).The expression of the OPN gene ***:The production of H,S,and CSE activity were de-creased and CSE gene expression was downregulated in rats with vascularcalcification.H2S can ameliorate vascular calcification,suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.

关键词： hydrogen sulfide cystathionine-lyase vascular calcification mRNA

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Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

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Acta Pharmacologica Sinica 2004年第03期25卷 87-92页

作者： Lin CHANG2,3.Jian-xin XU4,Jing ZHAO5,Yong-zheng PANG2,3.Chao-shu TANG2,3.Yong-fen QI5,6 2institute of cardiovascular Diseases,the FirstHospital,peking {3.,Beijing 10003. 3.0} of cardiovascular Diseases,peking {3.,Beijing 100083 4instituteof Biophysics,Chinese Academy of sciences,Beijing 100101 5Department of Physiology,health science {13.,peking {3.,Beijing 100083.china institute of cardiovascular Diseases the First Hospital Peking University institute of cardiovascular Diseases Peking University institute of Biophysics Chinese Academy of Sciences Beijing 100101 Department of Physiology Health Science Center Pe

AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) — hydrogen peroxide (H2O2) and superoxide anion (O2ˉ· )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P0.05 vs control). In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition, co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

关键词： homocysteine taurine vascular smooth muscle mitochondria reactive oxygen species

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补体相关性肾病诊断和治疗专家共识

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中华内科杂志 2024年第3期63卷 258-271页

作者：北京大学医学部肾脏病学系专家组赵明辉不详北京大学第一医院肾内科、北京大学肾脏病研究所北京100034

随着补体系统在各类肾脏疾病中的作用机制逐渐阐明,针对补体活化不同环节的药物相继出现,部分已应用于临床。但补体靶向治疗仍存在诸多问题。北京大学医学系补体相关性肾病诊断和治疗专家共识协作组在国内外肾脏疾病指南/共识的基础上,... 详细信息

随着补体系统在各类肾脏疾病中的作用机制逐渐阐明,针对补体活化不同环节的药物相继出现,部分已应用于临床。但补体靶向治疗仍存在诸多问题。北京大学医学系补体相关性肾病诊断和治疗专家共识协作组在国内外肾脏疾病指南/共识的基础上,结合最新证据制定了本共识,简述了补体相关性肾病的发病机制、诊断思路、补体靶向治疗与特殊致病微生物的疫苗免疫等方面的最新证据和建议,为补体相关性肾病的诊断和治疗提供参考。

关键词：补体相关性肾病诊断治疗补体抑制剂

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Receptor subtype involved in α-adrenergic receptor-mediated Ca2+ signaling in cardiomyocytes

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Acta Pharmacologica Sinica 2007年第7期 968-974页

作者： Da-li LUO~(2,3.4),Jian GAO~2,Lin-lin FAN~2,Yu TANG~2,You-yi ZHANG~3.Qi-de HAN~3.2 Department of Pharmacology,School of Chemical Biology and Pharmaceutical sciences,Capital university of Medical sciences,Beijing100069,{3. ~3.institute of cardiovascular science at the health science center,peking university,Beijing 100083.china

Aim:The enhancement of intracellular Ca2+signaling in response to α1-adrener-gic receptor （α1-AR） stimulation is an essential signal transduction event in theregulation of cardiac functions,such as cardiac growth,cardiac contraction,andcardiac adaptation to various *** present study was intended todetermine the role（s） of the α1-AR subtype（s） in mediating this ***:We evaluated the effects of subtype-specific agonists and antagonists of the α1-AR on the intracellular Ca2+signaling of neonatal rat ventricular myocytes usinga confocal ***:After being cultured for 48 h,the myocytesexhibited spontaneous local Ca2+release,sparks,and global Ca2+*** of the α1-AR with phenylephrine,a selective agonist of the α1-AR,dose-dependently increased the frequency of Ca2+transients with an EC50valueof 2.3.μmol/*** the α1A-AR subtype with 5-methylurapidil （5-Mu） inhi-bited the stimulatory effect of phenylephrine with an IC50value of 6.7 nmol/***,blockade of the α1B-AR and α1D-AR subtypes with chloroethylclonidineand BMY 73.8,respectively,did not affect the phenylephrine ***,thelocal Ca2+spark numbers were also increased by the activation of the α1-AR,andthis effect could be abolished selectively by *** importantly,A61603.anovel selective α1A-AR agonist,mimicked the effects of phenylephrine,but withmore potency (EC50value=6.9 nmol/L) in the potentiation of Ca2+transients,andblockade of the α1A-AR by 5-Mu caused abolishment of its ***:These results indicate that α1-adrenergic stimulation of intracellular Ca2+activityis mediated selectively by the α1A-AR.

关键词： α1-adrenergic receptor subtype cardiomyocyte Ca2+ signaling A61603

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p3. MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

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Acta Pharmacologica Sinica 2004年第3期25卷 12-16页

作者： Rui-mao ZHENG,Chang-jiang ZOU,Shi-gong ZHU2 Department of Physiology and Pathophysiology,health science center,{3. university,Beijing 100083.china Department of Physiology and Pathophysiology Health Science Center Peking University Beijing 100083 China

AIM: To investigate the roles of p3. mitogen-activated protein kinase (p3. MAPK) in the cardiovascular and behavioral responses induced by intracerebral ventricular injection (icv) of interleukin-1β (IL-1β) or footshock. METHODS: We examined the effects of p3. MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1β, or footshock after icv SB203.80 (a specific inhibitor of the p3. MAPK) with cardiovascular and Behavior Telemetry System in conscious SD rats. RESULTS: (1) IL-1β (icv) or footshock remarkably rise the mABP, and the maximal changes are (7.8±1.8) and (12.3.3.5) mmHg, respectively, which was abrogated by the pretreatment with p3. inhibitor SB203.80 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203.80 group with maximal changes (-7.6±1.1) counts/min after footshock. CONCLUSION: p3. MAPK plays an important role in the pres- sor response induced by central administration of IL-1β or footshock and change of motor activity after footshock in conscious rats.

关键词： mitogen-activated protein kinase p3. interleukin-1 blood pressure motor activity

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Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs

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Acta Pharmacologica Sinica 2004年第12期25卷 93-99页

作者： Ya-li ZHANG, Xiao-hong TAN2, Mei-fang XIAO, Hui LI, Yi-qing Mao, Xiao YANG2, Huan-ran TAN3. Department of Pharmacology, School of Basic Medical science, peking university {3. science center, Beijing 100083 2institute of Biotechnology Academy ofMilitary Medical science, Beijing 100071, china Department of Pharmacology School of Basic Medical Science Peking University Health Science Center Beijing 100083 China

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knock- out mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

关键词： animal disease model non insulin dependent diabetes mellitus type 2 diabetes mellitus glucokinase knockout mice

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Response synchronization: New progress in brain-visual information processing

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Chinese science Bulletin 1999年第16期44卷 1447-1458页

作者： ZHAO Songnian, XIONG Xiaoyun, YAO Guozheng and GUO Aike1. State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry , institute of Atmospheric Physics , Chinese Academy of sciences , Beijing 100029, china 2. Commission of the National Natural science Foundation of china , Beijing 100083, china 3. The center of Information science , peking university, Beijing 100871, china 4. Open Laboratory of Visual Information Processing , institute of Biophysics , Chinese Academy of sciences , Beijing 100101, china State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry Institute of Atmospheric Physics Chinese Academy of Sciences Beijing China Commission of the National Natural science Foundation of china Beijing China The center of Information science Peking University Beijing China Open Laboratory of Visual Information Processing Institute of Biophysics Chinese Academy of Sciences Beijing China

Studies on brain-vision have entered a new stage, after the stimulus-induced y synchronized oscillation of neuron group activities have been discovered in cat primary visual cortex. Naturally, how to understand the visual system became a very important methodological problem. From aspects such as information processing, nonlinear dynamics and neuronal network, some primary problems in vision studies have been deeply discussed, which are

关键词： neuron group (neural population) synchro-oscillation computational theory of vision response synchroniza-tion.

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Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling

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science china(Life sciences) 2011年第6期54卷 493-501页

作者： MA XiaoWei1,3.SONG Yao1,3.CHEN Chao1,3.FU YongNan1,3.SHEN Qiang2,3.LI ZiJian1,3.& ZHANG YouYi1,3.1institute of Vascular Medicine,peking university Third Hospital,Beijing 100191,{3. 2institute of cardiovascular science,peking university,Beijing 100191,{3. 3.ey Laboratory of Molecular cardiovascular sciences,Ministry of Education,Beijing 100191,{3. 1. institute of Vascular Medicine Peking University Third Hospital Beijing 100191 China3. Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China2. Institute of Cardiovascular Science Peking University Beijing 100191 China

Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac ***,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac ***,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-***,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in *** were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic *** function and remodeling were determined by echocardiography,micromanometry and ***,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes *** sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic *** disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of *** summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and *** findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mod

关键词： β-adrenoceptor reactive oxygen species NADPH oxidase cardiac hypertrophy cardiac fibrosis

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Implantable CMOS neuro-stimulus chip for visual prosthesis

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science china(Information sciences) 2011年第4期54卷 898-908页

作者： ZHANG Xu 1,PEI WeiHua 1,HUANG BeiJu 1,WANG ShuJing 1,GUAN Ning 1,GUO Kai 1,WANG Yu 1,GUI Qiang 1,CHEN Jin 1,WANG Kai 2,WU HuiJuan 2,LI XiaoXin 2,LI Kai 3.& CHEN HongDa 1 1 State Key Laboratory on Integrated Optoelectronics,institute of Semiconductors,Chinese Academy of sciences,Beijing 100083.china 2 Department of Ophthalmology,People’s Hospital of {3. university,Beijing 100044,china 3.Department of Epidemiology and Biostatistics,health science center,{3. university,Beijing 100083.china 1. State Key Laboratory on Integrated Optoelectronics Institute of Semiconductors Chinese Academy of Sciences Beijing 100083 China2. Department of Ophthalmology People’s Hospital of Peking University Beijing 100044 China3. Department of Epidemiology and Biostatistics Health Science Center Peking University Beijing 100083 China

A prototype chip with 2×2 pixels for implanting in blind patients affected by outer retinal degeneration is presented in this *** visual prosthesis chip imitates the degenerated photoreceptor cells,senses the incident light and stimulates the remaining healthy layers of retina or optic *** pixel integrates photodiode and stimulus pulse generator,converting the illumination on the eyes into 3.bit resolution bi-phasic current ***-chip charge cancellation modules are used to discharge each electrode site for tissue *** prototype chip is designed and fabricated in 0.18-μm N-well CMOS (complementary metal oxide semiconductor) 1P6M Mix-signal process,with a ±2.5 V dual voltage *** functionality of the fabricated chip is demonstrated on anesthetized *** responses in visual cortex are successfully evoked by the neuro-stimulus chip through an on-board trigger interface and flexible electrode.

关键词： biomedical microelectronics visual prosthesis functional electrical stimulation acute animal ex- periment electrical evoked potential (EEP) test

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