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Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide

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

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 Beijing 100083 China

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

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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~32 department of Pharmacology,School of Chemical Biology & Pharmaceutical sciences,Capital university of Medical sciences,beijing 100069,china 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,china department of Pharmacology School of Chemical Biology & Pharmaceutical Sciences Capital University of Medical Sciences Beijing 100069 China Institute of Cardiovascular science at health 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（IP3Rs）in the media-tion of cardiac intracellular Ca2+and hypertrophic growth remains *** with neonatal rat ventricular myocytes suggests that activation of IP3Rsmay be linked to α1adrenergic receptor（α1AR）increased stereotyped Ca2+sparkoccurrence and global Ca2+***,we hypothesized that Ca2+releasethrough IP3Rs was necessary for α1AR-stimulated cardiac ***:We used myoinositol 1,4,5-trisphosphate hexakis（butyryloxymethyl）ester（IP3BM）,a membrane-permeant ester of IP3,to activate IP3Rs directly,and Fluo 4/AM tomeasure intracellular Ca2+***:IP3BM(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,IP3R inhibitors,2-aminoethoxydiphenyl borateand Xestospongin C,abolished the IP3BM-induced Ca2+responses,and signifi-cantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cellsize,[3H]leucine incorporation and atrial natriuretic factor gene expression,dur-ing sustained（48 h）phenylephrine ***:These results,therefore,provide cellular mechanisms that link IP3R 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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Platelet-derived growth factor receptor-β in myocyte was upregulated by angiotensin Ⅱ

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Chinese science Bulletin 2002年第12期47卷 1015-1018页

作者： BAI Hua, SUN Yinping, XING Dongqi, LIU Jie & WU Lilingdepartment of physiology and Pathophysiology, peking university health science center, beijing 100083, china department of Cardiology, General Post and Telecom Hospital, beijing 100032, china Departmen department of physiology and Pathophysiology Peking University Health Science Center Beijing China department of Cardiology General Post and Telecom Hospital Beijing China department of Pathophysiology Xinxiang Medical College Xinxiang China

To observe the regulation of platelet-derived growth factor (PDGF) receptor-p in myocyte stimulated by angiotensin Ⅱ (AngII) at both integrated and cellular levels and reveal the signal transduction mechanism in cell, two kidneys, one clip (2K1C) renal hypertension were performed by placing a sliver clip around the left renal artery. Blood pressure and the ratio of left ventricular weight to body weight were measured at 4 and 8 weeks after operation. The content of Angll in heart was detected by radioimmunology assay; the protein level of PDGF receptor-β in heart was measured by Western blot analysis. The alteration of PDGF receptor-β stimulated by Angll and several inhibitors was observed on cultured neonatal rat ventricular myocyte (NRVM). The content of Angll in heart of 2K1C renal hypertensive rat at 4 and 8 weeks after operation was increased. Compared with sham group, 4 and 8 weeks after operation, PDGF receptor-p in heart of 2K1C group was upregulated by 100.3% and 127.1% (P 5),

关键词： angiotensin II PDGF receptor-p myocyte phospholipase C extracellular signal-regulated kinase.

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Hydroxyl radicals induced by quartz particles in lung alveolar macrophages: the role of surface iron

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Progress in Natural science:Materials International 2006年第10期16卷 1038-1044页

作者： LI Yi, ZHU Tong, GUO Xinbiao and SHANG Yu ( State Key Joint Laboratory for Environmental Simulation & Pollution Control, peking university, beijing 100871, china Occupational & Environmental health sciences, School of Public health, peking university health science center, beijing 100083, china) [a]State Key Joint Laboratory for Environmental Simulation & Pollution Control Peking University Beijing China [b]Occupational & Environmental health sciences School of Public Health Peking University Health Science Center Beijing China

Previous studies have shown that hydroxyl radical generation is a key step in the mechanism of pathogenic process caused by airborne particles to the lung. However, there is no direct evidence for dose-response relationship between airborne particles and hydroxyl radical generation. In this study, hydroxyl radicals generated in lung alveolar macrophages exposed to quartz particles were measured using a highly sensitive capillary electrophoresis-fluorescence detection method. The results demonstrated that quartz particles induced the generation of hydroxyl radical in a dose-dependent manner, and the amount of the hydroxyl radicals was 10-10 mol/10 cells. The viability of alveolar macrophages exposed to quartz particles decreased with the increase of quartz concentration, showing a clear dose-response relationship. Hydroxyl radical scavenger mannitol could increase the viability of quartz-treated cells, suggesting that hydroxyl radical contributed directly to cell death. In this study this contribution accounted for about 5%-20% of cell death. The hydroxyl radical generating potential was found to be related to surface iron content of the quartz particles.

关键词： inhalable quartz hydroxyl radical capillary electrophoresis dose-response relationship iron.

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Kinetics of thymocyte developmental process in fetal and neonatal mice

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Cell Research 2003年第4期13卷 265-273页

作者： SHI YUN XIAO, YAN LI, WEI FENG CHENdepartment of Immunology, School of Basic Medical sciences, peking university health science center, 38 Xueyuan Road, beijing 100083, china 1department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 China 1department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 China 1department of Immunology School of Basic Medical Sciences Peking University Health Science Center 38 Xueyuan Road Beijing 100083 China

Kinetics of thymocyte development in vivo during embryogenesis was pursued. The early development of thymocytes in the fetal and neonatal BALB/c mice was discontinuous, with four waves of cell proliferation occurring at fetal day (Fd) 14 to 17, Fd 18 to day (D) 1 after birth, D 2 to D 5 and D6 thereafter. The first three proliferation waves coincided with the generation of CD4/"CD8/" (DP), TCR+CD4/hiCD8-/lo (CD4 SP), and TCR+CD4-/loCD8int/hi (CD8 SP) thymocytes, respectively. The transition from DN to DP cells was further investigated and it was found out that there were two differential pathways via immature single positive (ISP) cells in the BALB/c mice, each functioning at different fetal ages. One is via TCR-CD4-CD8+ cells, occurring between Fd 15 and Fd 17 and the other is via TCR-CD4+CD8- cells, occurring from Fd 17 until birth. In contrast, the TCR-CD4-CD8+ pathway dominated overwhelmingly in the C57BL/6 mice. These findings shed new light on the hypothesis that the differential pathway preferenc

关键词： fetal thymus neonatal mice thymocyte ontogeny.

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Effects of estrogen on gastrocnemius muscle strain injury and regeneration in female rats

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Acta Pharmacologica Sinica 2004年第11期 105-110页

作者： Xin FENG, Guo-zhen LI, Sheng WANGdepartment of Occupational and Environmental health, Public health School, peking university health science center, beijing 100083, china

AIM: To study the effects of estrogen on muscle damage and regeneration after acute passive gastrocnemius muscle strain injury in female Sprague-Dawley rats. METHODS: Rats were divided into 5 groups: ovariectomized, strained and treated with low-dosage estradiol (20 μg/d) (Elow), treated with high-dosage estradiol (200 μg/d) (Ehigh), treated with oil placebo (Oil), strained with no ovariectomy (Strain), and sham operated with no strain and no ovariectomy (Con). Muscle damage index [plasma creatine kinase (CK)], antioxidant indexes [glutathione (GSH), Vitamin E (Vit E), total antioxidant capability (TAC)], and muscle regeneration index (desmin) were investigated at 7 d. RESULTS: The plasma CK activity increased but GSH, Vit E, and TAC levels decreased after muscle strain injury (Strain vs Con P5). Plasma CK activity was the greatest while GSH, Vit E, and TAC were the lowest in the Oil group among the five groups (P<0.01). Plasma CK in the Ehigh and Strain groups was lower than that in the Elow group

关键词： estrogen skeletal muscle muscle injury antioxidant regeneration desmin

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Urotensin Ⅱ increases endothelin production by vascular smooth muscle cells in rats

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Chinese science Bulletin 2002年第12期47卷 1007-1010页

作者： Ql Yongfen, BU Dingfang, YANG Jun, ZHANG Zhaokang, NIU Dadi, SHI Yanrong, ZHANG Zhenghao, TANG Chaoshu & DU JunbaoInstitute of Cardiovascular Diseases, The First Hospital of peking university, beijing 100083, china department of physiology, health science Institute of Cardiovascular Diseases First Hospital of Peking University Beijing 100083 China

The aim of this study was to observe the effects of urotensin Ⅱ (UII) on production of endothelin (ET) in rat aortic vascular smooth muscle cells (VSMC). Cultured VSMCs incubated with various concentrations of UII were used to measure the YSMC 3H-TdR incorporation, the amount of ET mRNA and ET production in VSMCs. In this work we found that UII (10-10-10-8 mol/L) promoted VSMC 3H-TdR incorporation (47%-83%, P5) to 112.8% (P 5.36 and 7.12 pg/mL (P < 0.01). After 8 h incubation, the ET content released from VSMCs was 12.6, 12.07 and 17.17 pg/mL (P < 0.01). In addition, it was found that BQ123, a specific ETA receptor antagonist, obviously decreased the VSMC DNA synthesis induced by

关键词： urotensin II endothelin mRNA peptide/interaction.

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β2 Adrenergic receptor on T lymphocytes and its clinical implications

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Progress in Natural science:Materials International 2009年第1期19卷 17-23页

作者： Xuelai Fan a,Yuedan Wang b,a peking university,School of Pharmaceutical sciences,beijing 100083.china b peking university,School of Basic Medical sciences,beijing 100083.china [a]peking university School of Pharmaceutical Sciences Beijing 100083 China [b]Peking University School of Basic Medical Sciences Beijing 100083 China

Sustained complex cross-talk between the immune system and the nervous system plays a vital role in retaining homeostasis in a healthy *** of the central regulatory mechanisms involved is the existence and functions of β2-adrenergic receptors(β2AR) on T *** article reviews research progress made recently,including the expression of adrenergic receptors on T lymphocytes,the structure and intracellular pathways of β2AR,the activation of β2AR by either endogenous or exogenous agonists,and the effect of β2AR stimulation on T cells which alters T cell proliferation,differentiation,cytokine production and T-helper-mediated antibody ***,we discuss the roles of β2AR played in the pathogenesis and treatment of autoimmune diseases.

关键词： Neuroimmunology β2-adrenergic receptor T cell Autoimmune

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