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5-Hydroxytryptamine-induced proliferation of pulmonary artery smooth muscle cells are extracellular signal-regulated kinase pathway dependent

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Acta Pharmacologica Sinica 2005年第5期26卷 563-567页

作者： Dan SONG,Huai-liang WANG~2.Shuang WANG,Xin-hua ZHANGDepartment of Clinical Pharmacology,china medical {2.,Shenyang 110001,china Department of Clinical Pharmacology China Medical University Shenyang China

Aim:To investigate the effect of 5-hydroxytryptamine transporter(5-HTT)inhibi-tor fluoxetine and antisense oligodeoxynucleotide(ODN)to extracelluar signal-regulated kinases(ERKs)on pulmonary arterial smooth muscle cells(PASMCs)proliferation induced by ***:Liposomal transfection was used tointroduce ODNs to ERK1/2.into cultured rat PASMCs and the transfection effi-ciency was measured by observing the uptake of the fluorecein isothiocynate(FITC)-labeled antisense ODN in *** effects of 5-HTT selective inhibi-tor fluoxetine and ODNs on the proliferation of PASMCs were evaluated by cellnumber counting and cell cycle analysis,and measured by microculture tetrazo-lium(MTT)assay and flow cytometry(FCM),***:Liposomesmediated the transfection of ODNs into PASMCs with high *** showed fluoxetine(10μmol/L,1 μmol/L,and 100 nmol/L)concentrationdependently inhibited the proliferation of PASMCs induced by 5-HT(1 μmol/L)*** proliferation rate of PASMCs by 5-HT was significantly inhibited bypretreatment with ERK1/2.antisense ODN(0.2.mol/L)from 2.1%±18% to 86%±5%(Pcell cycle distribution showed that theincrease of 5-HT induced S phase fraction(SPF)and proliferation index(PI)weresignificantly inhibited by fluoxetine(1μmol/L)or antisense ODN with SPF from36%±4% to 2.%±3% and 2.%±4%,and PI from 34%±2. to 2.%±2. and 2.%±2.,***:5-HTT mediates the mitogenic effect of 5-HT onPASMCs and the proliferation of PASMCs induced by 5-HT is dependent onERKs signal pathway.

关键词： antisense oligodeoxyribonucleotides serotonin membrane transport proteins pulmonary hypertension vascular smooth muscle fluxetine mitogen-activated protein kinases

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Genistein stimulates osteoblastic differentiation via p38 MAPK-Cbfa1 pathway in bone marrow culture

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Acta Pharmacologica Sinica 2007年第10期28卷 1597-1602页

作者： Qing-chuan LIAO~2.Zhou-sheng XIAO~(4,5),Yan-fang QIN~3,Hong-hao ZHOU~4~2.affiliated Children's hosp.tal,Nanjing {2. univer.ity,Nanjing 2.0008,china,~3 Department of Pathology,School of Medicine,Jinanuniver.ity,Guangzhou 510632.china ~4 Institute of Clinical Pharmacology,Central South univer.ity,Changsha 410078,china affiliated Children's hosp.tal Nanjing Medical University Nanjing China Institute of Clinical Pharmacology Central South University Changsha China Department of Pathology School of Medicine Jinan University Guangzhou China

Aim:To test the hypothesis that genistein stimulates the osteoblastic differentia-tion through the p38 mitogen activated protein kinase (MAPK)-core-binding fac-tor 1 (Cbfa1) ***:The activation of p38 MAPK was detected byWestern *** phosphatase (ALP) activ{2. and calcium depositionwere assessed for osteoblastic differentiation of bone marrow-derived mesenchy-mal stem cell (BMSC) *** expression of Cbfa1 was analyzed at both themRNA and protein *** activ{2. of Cbfa1 was detected by electrophoreticmobil{2. shift *** sialoprotein (BSP),ALP,osteocalcin (OC),andosteopontin (OPN) gene transcription were also evaluated by either RT-PCR orNorthern ***:Genistein (0.01-1 μmol/L) dose dependently led tothe rapid and sustained activation of the p38 MAPK pathway in mouse *** with genistein (1 μmol/L) resulted in increased ALP activ{2.and calcium deposition of BMSC cultures as a function of *** alsoenhanced Cbfa1 DNA binding activ{2. and promoted the expressions of Cbfa1itself as well as several Cbfa1-regulated genes,including ALP,BSP,OC,and *** treatment with p38 MAPK inhibitor (SB2.3580) diminished thegenistein-induced osteoblastic maturation and p38 MAPK-Cbfa1 activation inmouse BMSC ***:These results indicated that genistein couldstimulate the osteoblastic differentiation of BMSC cultures through the p38MAPK-Cbfa1 pathway.

关键词： bone marrow-derived mesenchymal stem cells core-binding factor 1 osteoblastic differentiation genistein mitogen-activated protein kinase

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Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guérin and lipopolysaccharide

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Acta Pharmacologica Sinica 2005年第6期26卷 745-752页

作者： Hua WANG, Wei WEI~3, Sheng-yi ZHANG~2. Yu-xian SHEN, Ni-ping WANG, Li YUE, Shu-yun XU Institute of Clinical Pharmacology, Anhui medical univer.ity, Hefei 2.0032.{2. ~2.epartment of Chemistry, Anhui univer.ity, Hefei 2.0039,{2.. Institute of Clinical Pharmacology Anhui Medical University Hefei China Department of Chemistry Anhui University Hefei China

Aim: Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guerin (BCG)/ lipopolysaccharide (LPS). Methods: The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate aminotransferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homo-genate were assayed by spectrophotometry. The content of tumor necrosis fac-tor (TNF) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2.yl]-2.5-diphenyltetra-zolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed. Results: In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5,10, or 2. mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF and IL-1 levels in the liver and inhibited the production of TNF and IL-1 by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed. Conclusion: MT-Se showed a hepatic protective action on immunological liver injury in mice.

关键词： melatonin selenium liver superoxide dismutase glutathione peroxidase nitric oxide tumor necrosis factor interleukin-1

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Tetramethylpyrazine protected photoreceptor {2.s of rats by modulating nuclear translocation of NF-κB

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Acta Pharmacologica Sinica 2005年第7期26卷 887-892页

作者： Jin-nan YANG~(2.3) Jin-mao CHEN~4 Lin LUO~4 Shao-chun LIN~4 Dai LI~4 Shi-xing HU~(4,5,6) 2.School of Pharmacy,Xinxiang medical College,Xinxiang 453003,china 4 Zhongshan Ophthalmic Centre,Sun Yat-sen {2.,Guangzhou 510060,china 5 Eye hosp.tal of china,Academy of Traditional Chinese Medicine,Beijing 100040,china School of Pharmacy Xinxiang Medical College Xinxiang China Zhongshan Ophthalmic Centre Sun Yat-sen University Guangzhou China Eye hosp.tal of china Academy of Traditional Chinese Medicine Beijing China

Aim:To evaluate the effect of tetramethylpyrazine(TMP)injection on retinaldamage induced by N-methyl-N-nitrosourea(MNU)in rats and on nuclear factor-kappa B(NF-κB)family ***:Female Sprague-Dawley(SD)ratswere randomly divided into groups:(i),control group;(ii),model group;and(iii),TMP-injection groups,in which the rats were subdivided into 40 mg/kg,80 mg/kgand 160 mg/kg *** were injected ip into 47-day-old SD rats once a *** 50 days of age,all rats in the model group and drug groups also received asingle ip injection of 60 mg/kg *** in group 1 received ip injection ofphysiological *** rats were killed at different times after MNU or physi-ological saline *** apoptotic index of photoreceptor cells was calcu-lated by TUNEL labeling;retinal damage was evaluated based on retinal thicknessand the expression of NF-κB family members was detected by Western ***:TMP injections,in a dose-dependent manner,suppressed photorecep-tor cell apoptosis and decreased its loss in the peripheral *** comparedwith the MNU-treated group,TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-κB/p65 protein level in the nucleus anddownregulated the IκBα protein level in the ***,no protectiveeffect of TMP injection on MNU-induced central retinal damage was ***:TMP injection partially protects against MNU-induced retinal dam-age by upregulating the nuclear translocation of p65 to inhibit photoreceptor cellsapoptosis.

关键词： tetramethylpyrazine photoreceptors methylnitrosourea apoptosis NF-kappa B retinitis pigmentosa

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Ginsenoside Rg1 inhibits proliferation of vascular smooth muscle cells stimulated by tumor necrosis factor-α

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Acta Pharmacologica Sinica 2006年第8期27卷 1000-1006页

作者： Zeng-chun MA Yue GAO~2.Yu-guang WANG Hong-ling TAN Cheng-rong XIAO Sheng-qi WANG Institute of Radiation Medicine Sciences,Academy of Military medical Sciences,Beijing 100850,china Institute of Radiation Medicine Sciences Academy of Military Medical Sciences Beijing China

Aim:To investigate the proliferation of vascular smooth muscle cells(VSMC)affected by ginsenoside Rg1 and further explore the molecular mechanism ofginsenoside Rg1 using ***:The proliferation of VSMC wasmeasured by MTS assay kit and flow *** alterations were ana-lyzed using two-dimensional electrophoresis and peptide mass *** proteins found in proteomics were confirmed by ***:The proliferation of VSMC was enhanced significantly after tumor necrosis fac-tor-α(TNF-α)treatment,and ginsenoside Rg1 treatment inhibited proliferation ina dose-dependent *** analysis showed 2. protein spots werechanged,including 17 spots that were increased and 7 spots that were *** Rg1 could restore the expression levels of these proteins,at leastpartly,to basic levels of untreated *** expression of G-protein coupledreceptor kinase,protein kinase C(PKC)-ζ,N-ras protein were decreased,whilecycle related protein p2. was increased by ginsenoside Rgl in TNF-α ***:PKC-ζ and p2. pathway might be the mechanism for inhibi-tory effects of ginsenoside Rg1 on proliferation of VSMC.

关键词： cell cycle ginsenoside Rg1 proteomics tumor necrosis factor-α vascular smooth muscle cells

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Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model

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Acta Pharmacologica Sinica 2007年第12期28卷 1947-1956页

作者： Xian-qing MAO~2.Yong WU~3,Ke WU~2.Ming LIU~2.Jing-fang ZHANG~4,Feng ZOU~2.Jing-ping OU-YANG~(2.5)~2.Department of Pathophysiology,medical College of Wuhan univer.ity,Hubei Provincial Key {2. of Allergy and Immune-RelatedDiseases,Wuhan 430071,china ~3 Division of Endocrinology and Diabetes,Department of Medicine,univer.ity of Oklahoma Health ScienceCenter,Oklahoma city,Oklahoma 73104,USA ~4 Department of Pathology and Physiology,Jingmen Vocational College,Jingmen 448000,china Department of Pathophysiology Medical College of Wuhan University Hubei Provincial Key Laboratory of Allergy and Immune-Related Diseases Wuhan China Division of Endocrinology and Diabetes Department of Medicine University of Oklahoma Health Science Center Oklahoma city USA Department of Pathology and Physiology Jingmen Vocational College Jingmen China

Aim:To examine the potential effects of Astragalus polysaccharide （APS） onhepatic endoplasmic reticulum （ER） stress in vivo and in vitro and its link withhypoglycemia activity,thus establishing the mechanism underlying the hypogly-cemic action of ***:The obese and type 2.diabetic KKAy mousemodel,which is the yellow offspring of the KK mice expressed Aygene (700mg·kg-1·d-1,8 weeks) and a high glucose-induced HepG2.cell model （2.0 μg/mL,2. h）were treated with *** oral glucose tolerance test was measured to reflexinsulin sensitivity with the calculated homeostasis model assessment （HOMA-IR） *** 1 （XhoI site-binding protein 1） transcription and splicing,an indica-tor of ER stress,was analyzed by RT-PCR and real-time *** expression andactivation of glycogen synthase kinase 3 beta （GSK3β）,an insulin signaling protein,was measured by Western ***:APS can alleviate ER stress in cul-tured cells in *** hyperglycemia status,systemic insulin sensitivity,fattyliver disease,and insulin action in the liver of diabetic mice were partly normalizedor improved in response to APS ***:Our results indicatethat APS enables insulin-sensitizing and hypoglycemic activity at least in part byenhancing the adaptive capacity of the ER,which can further promote insulinsignal ***,APS has promising application in the treatment of type2.diabetes.

关键词： Astragalus membranaceus polysaccharide type 2.diabetes mellitus insulin resistance endoplasmic reticulum stress

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SARS病毒及相关冠状病毒的生物学特征

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生物化学与生物物理学报 2003年第6期35卷 495-502页

作者：王承忠戚正武中国科学院上海生命科学院生物化学与细胞生物学研究所中国科学院上海生命科学院生物化学与细胞生物学研究所上海2.0031 复旦大学上海医学院生物化学与分子生物学系上海2.0032

重症急性呼吸综合征 (severeacuterespiratorysyndrome ,SARS) ,临床表现为非典型肺炎。2.0 0 2.底我国广东发现此种当时不明病因的疾病 ,此后在越南、中国香港、加拿大、美国等三十多个国家和地区也相继发现类似病例。由于SARS具有很... 详细信息

重症急性呼吸综合征 (severeacuterespiratorysyndrome ,SARS) ,临床表现为非典型肺炎。2.0 0 2.底我国广东发现此种当时不明病因的疾病 ,此后在越南、中国香港、加拿大、美国等三十多个国家和地区也相继发现类似病例。由于SARS具有很高的传染性 ,死亡率也高 ,各国和世界卫生组织 (WHO)对此病高度重视。WHO迅速建立起由全球 10个国家的 13个实验室组成的协作研究和监测网络。一种新型的冠状病毒 (coronavirus)被认为极可能是SARS的病原体 ,因为它满足了 6个科赫要点 (Koch’spostulates)。2.0 0 3年 4月 12. ,加拿大科学家首次公布了SARS病毒tor2.基因组序列。4月 16日 ,WHO正式确认SARS病毒是SARS的病原体。目前我国SARS的病情仍然十分严峻 ,现就SARS病毒及相关冠状病毒的生物学特征和可能的药物防治靶点作一综述。

关键词： SARS 非典型肺炎病毒冠状病毒生物学特征治疗

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Hormonal Regulation of Tissue-type Plasminogen Activator and Plasminogen Activator Inhibitor Type-1 Gene Expression in Cultured Mouse Sertoli cells

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Science china Chemistry 1993年第3期36卷 319-328页

作者：刘以训杜群胡召元 Ny tor Department of Endocrinology Institute of Zoology Academia Sinica Beijing 100080 PRC State Key labor.tor. of Reproductive Biology Institute of Zoology Academia Sinica Beijing 100080 PRC Unit for Applied cell and Molecular Biology Umea University S90187 Umea Sweden

We have demonstrated for the first time that (ⅰ) mouse Sertoli cells predominantly secrete tPA under the action of FSH and cAMP-generating agents, whereas Leydig cells mainly produce uPA; (ⅱ) Sertoli cells are also capable of secreting PAI-1, as well as FSH, growth factors and GnRH increase PAI-1 gene expression; (ⅲ) the increases in tPA and PAI-1 activities by different hormones in the conditioned media of Sertoli cells correspond to the increases in the levels of tPA and PAI-1 mRNA in the cultured cells, suggesting that the synthesis of the activator-inhibitor in mouse Sertoli cells is regulated at a transcriptional level and the tPA secreted by Sertoli cells may be involved in the spermatogenesis.

关键词： Sertoli cells tPA PAl-1 spermiation spermatogenesis.

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Anisodamine Inhibits Endotoxin-induced Tissue Factor Expression in Human Endothelial cells

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Journal of Huazhong univer.ity of Science and Technology(medical Sciences) 2002年第4期22卷 273-275页

作者：阮秋蓉宋建新邓仲端 DepartmentofPathology DepartmentofInfectiousDisease

By study on the effect of anisodamine on lipopolysaccharide- induced expression of tissue factor(TF) in vascular endothelial cells(EC) ,the mechanism of anisodam ine antithrom bosis,as well as in the treatm ent of bacteraemic shock was *** umbilical vein endothelial cells (HUVECs) were cultured by trypsin digestion m *** activity was measured in the lysates of HUVEC by using a single step clotting *** m RNA expression was detected by Northern *** order to evaluate a possible contribution of the nuclear factor (NF) -κB pathway on the effects observed,electrophoretic mobility shift assays(EMSA) were performed using nuclear extracts from HU VECs and NF- κB- binding *** results showed that treatment of HUVEC with L PS resulted in a significant increase in TF *** dose- dependently inhibited L PS- induced upregulation of *** effects was also confirm ed on the level of specific TF m RNA expression by Northern *** ore,EMSA showed that anisodamine com pletely abolished L PS- induced NF-κB DNA binding activity in nuclear ex- tracts from HUVECs treated with L PS together with *** results suggest thataniso- damine counteracts endothelial cell activation by inhibiting L PS- induced TF expression in these *** interference with the NF- κB pathway might- at least in part- contribute to this effect. The ability of anisodamine to counteract L PS effect on endothelial cells m ight be one underlying m echanism explaining its antithrombosis and efficacy in the treatment of bacteraemic shock.

关键词： Anisodamine endothelial cell tissue factor lipopolysaccharide shock nuclear fac- tor-κB

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Effects of human umbilical cord serum on proliferation and insulin content of human fetal islet-like cell clusters

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Hepatobiliary & Pancreatic Diseases International 2004年第1期3卷 144-148页

作者： Dong Xia, Hong-Yuan He, Zheng-Ming Lei, Pei-Ming Zhang and Yong Guo Luzhou, china Department of General Surgery, West china {2. , and Department of Surgery, Fifth {2. of Sichuan Province , Chengdu 610041, china Department of Histology and Em- bryology , and Hepatobiliary and Pancreatic labor.tor. , Luzhou medical College, Luzhou 646000, china Department of General Surgery West China Hospital Chengdu 610041 China. juliahhy@***

BACKGROUND: Type 1 diabets is an autoimmune disease caused by the destruction of pancreatic β-cell with an in- creased incidence worldwide in the closing decades of the 2.th century. This study was to investigate the effects of human umbilical cord serum (UCS) on the proliferation and function of human fetal islet-like cell clusters (ICCs) in vitro. METHODS: Eight fresh pancreatic glands obtained after in- duction of labor with water bag were mildly exposed to col- lagenase V, and the digested cells were cultured in a RPMI- 1640 medium plus 10% pooled UCS or fetal calf serum (FCS) to permit cells attachment and outgrowth of ICCs. RESULTS: In 8 consecutively explanted glands, develop- ment and proliferation of ICCs were observed. In the pre- sence of FCS, the outgrowth of ICC took place on the top of a flbroblast monocellular layer. UCS affected less growth of fibroblasts and increased the formation of ICCs about four-fold compared with explants from the same glands maintained in FCS. In both UCS and FCS, the insulin con- tent of the medium was variable to a certain extent and progressively declined from day 2.to day 6. Dithizone- stained ICCs in UCS suggested that most cell clusters were islet cells ( β-cells), and the purity of islets was estimated 80%-90%. The ultrastructure of the cultured cells showed a large number of granule-containing cells, most of which were identified as β-cells. CONCLUSION: We conclude that in comparison with ex- plants with FCS, the yield of ICCs and purification of islet cells are markedly increased by UCS and may facilitate the proliferation of pancreatic β-cells intended for islet trans- plantation.

关键词： islet cell culture islet-like cells clusters umbilical cord serum fetal calf serum

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