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Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats

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Acta Pharmacologica Sinica 2006年第8期27卷 971-980页

作者： Xiao-hui LI~2 Jun-bao DU~(2,6) Ding-fang BU~3 Xiu-ying TANG~4 Chao-shu TANG~5 ~1department of Pediatrics,peking university First Hospital,Key Laboratory of Molecular Cardiovascular Diseases,Ministry of Education ~3 Laboratory center ~4Laboratory of Electron Microscopy,peking university First Hospital,beijing 100034,china ~5department of physiology,peking university health science center,beijing 100083,china department of Pediatrics Peking University First Hospital Key Laboratory of Molecular Cardiovascular Diseases Ministry of Education Beijing China Laboratory center Peking University First Hospital Beijing China Laboratory of Electron Microscopy Peking University First Hospital Beijing China department of physiology Peking University Health Science Center Beijing China

Aim:To explore the possible role of endogenous hydrogen sulfide （H2S）,a novelgasotransmitter,in the pathogenesis of pulmonary vascular structural remodeling（PVSR） induced by high pulmonary blood ***:Thirty-two Sprague-Dawley male rats were randomly divided into sham,shunt,sham+NaHS （a H2Sdonor） and shunt+NaHS *** in shunt and shunt+NaHS groups under-went an abdominal aorta-inferior vena cava shunt,and rats in shunt+NaHS andsham+NaHS groups were intraperitoneally injected with *** was inves-tigated using optical microscope and transmission electron *** H2S was evaluated by sulfide-sensitive *** oxide synthase（NOS）,heme oxygenase （HO-1）,proliferative cell nuclear antigen （PCNA） andextracellular signal-regulated kinase （ERK） activation were analyzed by ***:After 11 weeks of shunting,PVSR developed with a decrease inlung tissue H2S production and an increase in nitric oxide （NO）.However,lungtissue carbon monoxide （CO） did not *** the treatment with NaHS for11 weeks,H2S donor ameliorated PVSR and downregulated PCNA expression andERK activation with an increase in lung tissue CO production and HO-1 proteinexpression but a decrease in NO production,NOS activity and eNOS proteinexpression in shunted ***:H2S exerted a regulatory effect on PVSRinduced by high pulmonary blood ***,H2S down-regulated theERK/MAPK signal pathway,inhibited the NO/NOS pathway and enhanced theCO/HO pathway in rats with high pulmonary blood flow.

关键词： hydrogen sulfide pulmonary hypertension structure remodeling nitric oxide/nitric oxide synthase carbon monoxide/heme oxygenase

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Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide

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Acta Pharmacologica Sinica 2004年第6期25卷 131-136页

作者： Qi-zhen CAO, Zhi-bin LIN1 department of Pharmacology, health science center, peking university, beijing 100083, china department of Pharmacology Health Science Center Peking University 100083

AIM: To investigate the antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide (GLPP). METHODS: Antitumor effect of GLPP was observed in tumor-bearing mice in vivo. At the same time, the effects of GLPP on proliferation of tumor cells and human umbilical cord vascular endothelial cell (HUVEC) were detected by MTTassay in vitro. Subsequently, spleen lymphocytes proliferation of nude mice was stimulated by LPS or ConA. To investigate the anti-angiogenic effect of GLPP, GLPP 80 μg per disc and GLPP-treated serum 10 μL per disc were added to the chick chorioallantoic membrane (CAM) respectively in vivo. RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of Sarcoma 180 in BALB/c mice markedly by 35.2 %, 45.2 %, and 61.9 %, respectively. GLPP which was directly added to the cultured medium did not inhibit PG cell proliferation in vitro; but GLPP-treated serum 50, 100, 200 mg/kg potently inhibited PG cell proliferation by 22.5 %, 26.8 %, and 30.3 %, respectively; and reduced the xenograft (human lung carcinoma cell PG) in BALB/c nude mice greatly in vivo by 55.5 %, 46.0 %, and 46.8 %, respectively. Lymphocytes proliferation of nude mice could be stimulated by LPS 5 mg/Lbut not by ConA 2.5 mg/L, indicating that GLPP could not promote the T lymphocyte proliferation and neutral red phagocytosis of peritoneal macrophages of nude mice. The CAM assay showed that GLPP and GLPP-treated serum had anti-angiogenic effect. GLPP (1, 10, and 100 mg/L) inhibited HUVEC proliferation in vitro with the inhibitory rate of 9.4 %, 15.6 %, and 40.4 %, respectively. CONCLUSION: GLPP has antitumor and anti- angiogenic activity. The anti-angiogenesis of GLPP may be a new mechanism underlying its anti-tumor effects.

关键词： Ganoderma lucidum polysaccharides sarcoma 180 adenocarcinoma lung neoplasms lympho- cyte proliferation peritoneal macrophages angiogenesis nude mice

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p38 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,peking university,beijing 100083,china department of physiology and Pathophysiology Health Science Center Peking University 北京 100083

AIM: To investigate the roles of p38 mitogen-activated protein kinase (p38 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 p38 MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1β, or footshock after icv SB203580 (a specific inhibitor of the p38 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 p38 inhibitor SB203580 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203580 group with maximal changes (-7.6±1.1) counts/min after footshock. CONCLUSION: p38 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 p38 interleukin-1 blood pressure motor activity

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Effects of Ganoderma lucidum polysaccharides on proliferation and cytotoxicity of cytokine-induced killer cells

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Acta Pharmacologica Sinica 2005年第9期26卷 1130-1137页

作者： Xiao-ling ZHU Zhi-bin LIN department of Pharmacology,School of Basic Medical science,peking university health science center,beijing 100083,china department of Pharmacology School of Basic Medical Science Peking University Health Science Center Beijing 100083 China

Aim:To study the effects(and the mechanisms thereof)of Ganoderma lucidumpolysaccharides(G/-PS)on the proliferation and the anti-tumor activity of cytokine-induced killer(CIK)cells,and to make use of CIK cells as a means to investigatethe interactions between Gl-PS and ***:CIK cells were preparedby using the standard protocol as a positive *** groups alsounderwent the standard protocol,except that Gl-PS(400 mg/L or 100 mg/L)wasadded and the dose of anti-CD3 and interleukin-2 they received was reduced by50% and 75%,*** negative controls,Gl-PS in the experimentalprotocol was replaced with soluble starch or methylcellulose(400 mg/L or 100 mg/L).CIK cell proliferation,cytotoxicity,and phenotype were determined by using theTrypan blue exclusion method,MTT assay,and flow ***:Bysynergizing cytokines,Gl-PS(400 mg/L or 100 mg/L)could decrease the amountof cytokine in lymphokine activated killer(LAK)cells and CIK cells culture,buthad no significant effect on the proliferation,cytotoxicity,or phenotype of LAKcells,or CIK cells induced by cytokines at higher doses alone,in which CIK cellsexpanded about 80-fold and the main effectors,CD3~+NK1.1~+ cells,expanded bymore than 15%.The cytotoxicity of CIK cells in experimental groups was 79.3%±4.7%,76.9%±6.8% versus the positive control 80.7%±6.8% against P815(P>0.05)and 88,9%±5.5%,84.7%±7.9% versus the positive control 89.8%±4.5% againstYAC-1(P>0.05).The activity of GI-PS could mostly be blocked by ***:GI-PS was shown to be a promising biological response modifier andimmune *** effect of GI-PS on CIK cells is possibly mediated prima-rily through complement receptor type 3.

关键词： Ganoderma lucidum polysaccharides cell proliferation cytotoxicity immunomodula-tion

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Taurine inhibits ischemia/reperfusion-induced compartment syndrome in rabbits

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Acta Pharmacologica Sinica 2005年第7期26卷 821-827页

作者： Ji-xian WANG~(2,3) Yan LI~2 Li-ke ZHANG~4 Jing ZHAO~5 Yong-zheng PANG~(2,3) Chao-shu TANG~(3,5) Jing ZHANG~(2,3,6) 1 Institute of Cardiovascular Disease Research,The First Hospital of peking university,beijing 100034,china 3 Key Laboratory of Molecular Cardiovascular science,Ministry of Education,beijing 100083,china 4 department of Pathophysiology,Capital Institute of Medicine,beijing 100054,china 5 department of physiology health center of Medical sciences,peking university,beijing 100083,china Institute of Cardiovascular Disease Research The First Hospital of Peking University Beijing China Key Laboratory of Molecular Cardiovascular science Ministry of Education Beijing China department of Pathophysiology Capital Institute of Medicine Beijing China department of physiology Health Center of Medical Sciences Peking University Beijing China

Aim:To investigate effects of taurine on ischemia/reperfusion(I/R)-induced com-partment syndrome in rabbit hind ***:Rabbits underwent femoralartery occlusion after ligation of branches from terminal aorta to femoral *** a 7-h ischemia,reperfusion was established with the use of heparinizedpolyethylene *** received taurine(1 g/kg)or normal saline(control)by iv infusion 10 min before shunt *** reperfusion,anterior com-partment pressure(ACP)was monitored continuously in the left lower *** muscle triphenyltetrazolium chloride(TTC)level,taurine contentand myeloperoxidase activity were *** stress was induced in thein vitro gastrocnemius muscle slices by free radical generating systems(FRGS),and the malondialdehyde content was measured in presence or absence of ***:After 7 h of ischemia,none of the parameters that we measured weredifferent from those before ischemia,except that TTC reduction decreased by80%.In the control group,after 2 h of reperfusion,ACP increased 4.5-fold,andgastrocnemius muscle taurine content was reduced by 33%.In taurine-treatedanimals,at 2 h reperfusion,the mean arterial blood pressure and heart rate wereincreased,by 6% and 10%.ACP decreased by 39%,muscle edema decreased by16%,TTC reduction increased by 150%,and lactate dehydrogenase decreased by36% compared to control *** and muscle taurine content increased by70% and 88%,*** the taurine-treated group,at 2 h repeffusion,plasmamalondialdehyde and conjugated diene content were decreased by 38% and 23%,respectively,and muscle malondialdehyde and conjugated diene content decreasedby 22% and 30%,respectively compared to the control *** 2 h reperfusion,myeloperoxidase activity was increased 3.5-fold in control *** the in vitrostudy,taurine decreased malondialdehyde content in muscle slices incubatedwith hypochlorous acid in a dose-dependent manner,but there was no changewhen incubated

关键词： taurine compartment syndromes reperfu sion injury

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Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus

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Cell Research 2007年第6期17卷 556-564页

作者： Peng Yang Bo Li Ping Lv Yan Zhang Xiao-Ming Gao, department of Immunology, peking university health science center, peking university, 38 Xueyuan Rd, beijing 100083, china department of Immunology Peking University Health Science Center Peking University Beijing China

Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ampleevidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This studywas undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactiveT cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after γ-ray irradiation, wereable to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able tostimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) weremuch more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and Bcells, but not DCs, was sensitive to γ-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were ableto block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Ourdata suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotalrole in keeping the momentum of autoimmune responses leading to autoimmune diseases.

关键词： SLE T cells antigen presenting cells

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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3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 university,beijing 100034 3Institute of Cardiovascular Diseases,peking university,beijing 100083 4Instituteof Biophysics,Chinese Academy of sciences,beijing 100101 5department of physiology,health science center,peking university,beijing 100083,china Institute of Cardiovascular Diseases the First Hospital Peking University 北京 100034 Institute of Biophysics Chinese Academy of Sciences 北京 100101 department of physiology Health Science Center Peking University 北京 100083

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 (P5, 10, and 20 mmol/L) significantly antago- nized 0.5 mmol/L homocysteine-induced H2O2generation in VSMC in a concentration dependent manner (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 (P5), 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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Laser-field-induced magnon amplification in a magnetic semiconductor quantum well under an external magnetic field

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Journal of university of science and Technology beijing 2003年第5期10卷 69-72页

作者： Peng FengPhysics department, university of science and Technology beijing, beijing 100083, china Phys. Dept. Univ. of Sci. and Technol. Beijing Beijing 100083 China

The laser-field induced magnon amplification in a magnetic semiconductorquantum well under an external magnetic field was discussed, it is shown that when the laserfrequency is near to the electron cyclotron frequency, no matter how weaker the laser field is, themagnon amplification always occurs. In case of fixed laser frequency, the optical absorption ofmagnons obeys the definite selection rule to the laser field strength. The rate of change of magnonoccupation is calculated, and the amplification condition is given.

关键词： magnon amplification magnetic semiconductor quantum well laser field

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Hormones and cancer

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Cell Research 2007年第4期17卷 277-279页

作者： Yongfeng Shang~1 ~1department of Biochemistry and Molecular Biology,peking university health science center,38 Xueyuan Rd,beijing 100083,china department of Biochemistry and Molecular Biology Peking University Health Science Center Beijing China

Estrogen exhibits a broad spectrum of physiologicalfunctions ranging from regulation of the menstrual cycleand reproduction to the modulation of bone density,brainfunction,and cholesterol ***,estrogenis also associated with pathological complications par-ticularly with the onset of gynaecological malignanciesincluding breast cancer and endometrial cancer;estrogenis now considered to be a classical etiological factor forbreast cancer and endometrial *** the early 1970s,it was reported that there was a 20-35% increase in incidence of endometrial cancer in WesternCaucasian women who had undergone estrogen therapy[1].Subsequently,a variety of clinical and epidemiologi-cal investigations,with support from studies in cell cultureand animal models,have demonstrated the association ofestrogen with the development and/or progression of *** 2002,the US National Toxicology Programlisted steroidal estrogens as carcinogens for the first *** report cites data from human epidemiologic studies thatshow an association between estrogen replacement therapyand an increase in the risk of endometrial cancer,as well asa less consistent increase in the risk of breast cancer.

关键词： gene NSABP Hormones and cancer ERE SERMs

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Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 527-535页

作者： LLian LI~2 Li-ke ZHANG~5 Yong-zheng PANG~(2.4) Chun-shui PAN~(3.4) Yong-fen QI~(3.4) Li CHEN~4 Xian WANG~(3,4) Chao-shu TANG~(3,4) Jing ZHANG~(2,4,6) ~2Institute of Cardiovascular Research,peking university First Hospital,beijing 100034,china:~3department of physiology and Pathophysiology,peking university health science center,beijing 100083,china ~4Key Laboratory of the Ministry of Education on Molecular Cardiology,beijing 100083,china:~5department of Pathophysiology,Capital university of Medicine,beijing 100054,china Institute of Cardiovascular Research Peking University First Hospital Beijing China department of Pathophysiology Capital University of Medicine Beijing China Key Laboratory of the Ministry of Education on Molecular Cardiology Beijing China department of physiology and Pathophysiology Peking University Health Science Center Beijing China

Aim:To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial ***:Rats were subcu-taneously injected with isoproterenol （ISO;20,10,and 5 mg/kg） on d 1,2 and 3,respectively,and then 3 mg/kg for the next 7d with or without ghrelin or des-octanoyl-ghrelin （100μg/kg,twice daily）.Plasma ghrelin and growth hormonelevels were assayed using radioimmunoassay *** hormone secreta-gogue receptor （GHSR） and ghrelin mRNA were determined using *** binding capacity and the affinity for [3H]ghrelin were determined by re-ceptor binding ***:Compared with controls,ISO-treated rats showedsevere myocardial injury,cardiomegaly,infarction-like necrosis and massive fi-brosis with increases in irradiated-ghrelin （ir-ghrelin） content in plasma by 67%and myocardia by 66% and in the mRNA level in the myocardia by 93% （P5% （P5-fold （P<0.01）,with ghrelinadministration as compared with that in controls,but was unaltered in the des-octanoyl ghrelin ***:Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial *** protective effect of ghrelinagainst ISO-induced cardiac function injury and fibrosis was more potent thanthat of des-octanoyl ghrelin,which suggests that ghrelin could be an endog

关键词： ghrelin des-octanoyl ghrelin myocardium fibrosis isoproterenol

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