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王银叶

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王银叶,女,教授,硕士生导师。1982年北京医学院药学系(现北京大学药学院)毕业。1982-1987在本校药学系任教,1987-1988 在美国默沙东公司微生物系进修,从事蛋白酶抑制剂,细胞因子抑制剂和受体拮抗剂的新药筛选研究。1988-1994在本校药学院任教,从事心血管药理的研究工作,包括钙拮抗剂、PAF受体拮抗剂及小分子多肽心血管活性研究,先后任讲师、副教授。1995年在美国肯塔基州立大学生化系进修,从事分子生物学的研究工作。1995年至今在本校药学院分子与细胞药理系从事药理教学和心血管药理和基因工程药学的研究工作。2002年任北京大学药学院365bet体育游戏_365线上体育_365体育投注+ribo88教授。承担了多项科技部项目、自然科学基金面上和重点项目,发表科研论文四十余篇,获得发明专利五项。

通讯地址:北京市海淀区学院路38号、药物依赖所楼6层

邮编:100191

Tel: (010)-8280 2652

E-mail: wangyinye@bjmu.edu.cn

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主要研究方向:

1.心血管细胞药理

血管内皮细胞是血液和平滑肌细胞之间的生理屏障,承担着重要的生理功能,血管内皮功能异常会促成多种心血管疾病如高血压、糖尿病、血栓性疾病及动脉粥样硬化的发生和发展,维护和改善血管内皮细胞功能对于预防和治疗这些疾病有重要意义。课题组从事内皮细胞相关研究,旨在寻找新的具有内皮细胞保护作用的化合物,研究药物对内皮细胞与心血管疾病关系的影响,以及发现药物新的治疗靶点。心肌缺血、脑缺血以及缺血治疗时的再灌注都会引起严重的组织细胞损伤,减少或防止缺血和再灌注引起的细胞损伤对于维护器官的功能,减轻和改善心、脑缺血引起的神经功能异常至关重要。课题组从事心肌细胞和神经元细胞药理的相关研究,旨在寻找新的心肌细胞和神经细胞保护药物,阐明药物的作用机制,以及发现新的药物作用靶点。

2.血栓相关疾病药理 血栓栓塞性疾病,如心肌梗死、脑卒中、深部静脉血栓形成等,已成为世界范围内致死率或致残率最高的疾病之一。课题组从事抗血小板新药、抗凝血新药、和溶血栓新药的药理学研究,系统的建立了抗血小板、抗凝血和溶血栓药的分子与细胞水平实验方法和临床前药理评价的动物研究模型;进行新药筛选、临床前药效学和药物作用机制研究。这些研究对于血栓性疾病相关新药的发现和阐明已有药物特别是中药和天然药物的作用机制有重要意义。

3.心血管活性蛋白/多肽的基因工程药学及药理学研究 基因工程药物因为其疗效好,副作用小,应用范围广泛而成为全球新药研发的热点。基因工程药学是本课题组在本院首先开展的研究领域,旨在通过结构生物学、组合生物学、计算机辅助药物设计以及药理学等跨学科的交叉合作寻找具有应用价值的新型心血管活性蛋白/多肽。

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主要研究内容

1. 血栓相关药物的发现和新靶点研究,抗血栓药动物模型的研究

2. 影响血管内皮细胞功能的药物发现及机制研究

3. 抗心肌缺血药的细胞及动物模型研究,新药及机制研究

4. 抗脑缺血药的细胞及动物模型研究,新药及机制研究

5. 抗高血压药药效及机制研究

6. 调血脂抗动脉粥样硬化药药效学研究

7. 蛋白及多肽类药物的基因工程药学及药理学研究

在研基金

国家自然科学基金面上项目:针对脑缺血损伤多环节损伤的融合蛋白分子设计、制备及活性研究

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发表论文:

  1. 1. Yuanjun Zhu#, Yuanqing Gao#, Danping Zheng#, Mengyang Shui, Kuai Yu, Xiaoyan liu, Yuan Lin, Li Su, Wenxing Yang, Yinye Wang*. Design and evaluation of EphrinA1 mutants with cerebral protective effect. Scientific Reports, 2017; 7: 1881.
  2. 2. Yuanjun Zhu#, Mengyang Shui#, Xiaoyan Liu, Wenhui Hu*, Yinye Wang*.Increased autophagic degradation contributes to the neuroprotection of hydrogen sulfide against cerebral ischemia/reperfusion injury. Metabolic Brain Disease, 2017, doi: 10.1007/s11011-017-0014-4.
  3. 3. Yuanjun Zhu#, Tongliang Zhou#, Lingfei Yang, Lan Yuan, Lei Liang*, Ping Xu*.Revelation of the dynamic progression of hypoxia-reoxygenation injury by visualization of the lysosomal hydrogen peroxide. Biochemical & Biophysical Research Communication, 2017, 486 (4):904-908.
  4. 4. Yuanjun Zhu#, Yuan Lin#, Xiaoyan Liu, Wenhui Hu*, Yinye Wang*. Identification of AcAP5 as a novel factor Xa inhibitor with both direct and allosteric inhibition. Biochemical and Biophysical Research Communications, 2017, 483(1):495-501.
  5. 5. Yuanjun Zhu#, Ruyi Li#, Yuan Lin, Mengyang Shui, Xiaoyan Liu, Huan Chen, Yinye Wang*. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting. Scientific Reports. 2016; 6: 29895.
  6. 6. ?Mengyang Shui, Xiaoyan Liu, Yuanjun Zhu*, Yinye Wang*. Exogenous hydrogen sulfide attenuates cerebral ischemia-reperfusion injury by inhibiting autophagy in mice. Canadian Journal of Physiology and Pharmacology, 2016, 94(11): 1187-1192,
  7. 7. Yuanjun Zhu, Yuan Lin, Aihua Liu, Mengyang Shui, Ruyi Li, Xiaoyan Liu, Wenhui Hu, Yinye Wang*. Structure-guided creation of AcAP5-derived and platelet targeted factor Xa inhibitors. Biochemical Pharmacology. 2015, 95(4):253-62.
  8. 8. Hongfei Li, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Yinye Wang*. Magnolol derivative 002C-3 protects brain against ischemia–reperfusion injury via inhibiting apoptosis and autophagy, Neuroscience Letters, 2015, 588:178-183
  9. 9. Kun Hu, Xiaoyan Liu, Yuanjun Zhu, Jingliang Zhang, Ye Liu , Yinye Wang*.Antithrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo.J. Chin. Pharm. Sci. 2014, 23 (11), 760–764
  10. 10. Yuanjun Zhu, Qixin Bu, Xiaoyan Liu, Wenhui Hu, and Yinye Wang*. Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats. PLoS One. 2014; 9(3): e93334.
  11. 11. Qixin Bu, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Yinye Wang*, w007B protects brain against ischemia-reperfusion injury in rats through inhibiting inflammation, apoptosis and autophagy. Brain Res. 2014,1558:100-8.
  12. 12. Yuanjun Zhu, Aihua Liu, Xiaoyan Liu and Yinye Wang*. Engineering Novel Anticoagulant Proteins by Motif Grafting. Protein Pept Lett. 2014, 21(2):159-63.
  13. 13. Yanan Zhu, Yuanjun Zhu, Qixin Bu, Xiaoyan Liu, Yinye Wang*. rAcAP5: high-yield strain screening, expression, purification and thrombolytic effect evaluation in rat embolic middle cerebral artery occlusion model. J. Chin. Pharm. Sci. 2014, 23 (1), 22-27.
  14. 14. Peng Zhang, Xiaoyan Liu , Yuanjun Zhu , Shizhong Chen, Demin Zhou, Yinye Wang*, Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-kB activation and cytokine production of glial cells, Neuroscience Letters, 2013,534, 123–127
  15. 15. Zhenyu Hu, Xiling Bian, Xiaoyan Liu, Yuanjun Zhu, Xiaoyi Zhang, Shizhong Chen, Kewei Wang, Yinye Wang. Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction. Brain Res. 2013; 1491:204-12.
  16. 16. Aihua Liu, Yuanjun Zhu, Xiaoyan Liu, Yinye Wang*.Expression, purification and evaluation of N-terminal domain of AcAP5 with Factor Xa inhibitory activity. J. Chin. Pharm. Sci. 2013, 22 (3), 205–208
  17. 17. Xiumei Liu, Xiaoyan Liu, Yinye Wang*. Methoxyl methyl ether isoamylene quercetin, a quercetin derivative, protects rat aorta endothelial cells against oxidation and apoptosis. J. Chin. Pharm. Sci. 2013, 22 (4), 289–292
  18. 18. 刘晓岩, 张超逸,王银叶*,车庆明, 6,7-二乙酰黄芩素对四氯化碳和D-氨基半乳糖所致的急性肝损伤的保护作用. 中国新药杂志,2012,21(13):1517-19.
  19. 19. 杨爽,刘晓岩,胡振宇,陈世忠,王银叶* ,和厚朴酚通过抑制脑MPTP开放和调节PARP-1活性保护全脑缺血的作用研究,中国药理学通报,28(2)218-221, 2012
  20. 20. Shuang Ding, Xiaoyan Liu, Yuanjun Zhu, Yinye Wang*. Thrombolytic effect of rAcAP5 and its mechanism. JCPS?2012, 21?(1):?70-75.
  21. 21. 王银叶,丁双,刘晓岩,朱元军. 犬钩虫抗凝肽及其突变体在制备溶血栓药物中的应用途.201110106956.6(专利)
  22. 22. Xiumei Liu, Xiaoyan Liu, Yinye Wang*, Shizhong Chen*. Cyclovirobuxine D inhibits blood coagulation and venous thrombosis. J Chin Pharmaceut Sci, 2010; 19(2):120-124
  23. 23. 胡涛,刘晓岩,郭宏宝,王银叶.三种中药活性部位对H2O2致PC12细胞损伤保护作用的比较研究.中国临床药理学与治疗学2010,1:53-58
  24. 24. Zhiyu Tang, Ming Zhao, Changling Li, Yinye Wang*, Shiqi Peng*, Polyaspartoyl·L-arginine inhibits platelet aggregation through stimulation of NO. Eur J Pharmacol 2008; 588: 41-46
  25. 25. Jian Yang, Zhiyu Tang, Yinye Wang*, Shiqi Peng*. Polyaspartoyl L-arginine protects endothelial cells against injury. Eur J Pharmacol 2008; 599: 96-101
  26. 26. Zhiyu Tang, Jian Yang, Xiaoyan Liu, Yinye Wang*, Shiqi Peng*. Polyaspartoyl·L-arginine enhances prostacyclin synthesis in rat aorticendothelial cells Eur J Pharmacol ?2008; 601: 124-128
  27. 27. 李洁璇,张晓雪,王银叶. 新型多肽bg115-2体外对凝血因子X的抑制作用.中国新药杂志2008,17(8)656-660
  28. 28. Die Hu, Xiaoyan Liu, Yinye Wang*, Shizhong Chen*. Cyclovirobuxine D ameliorates acute myocardial ischemia by KATP channel opening, nitric oxide release and anti-thrombosis. Eur J Pharmacol 2007;569: 103-109
  29. 29. Xiaoxue Zhang, Shizhong Chen, Yinye Wang*. Honokiol up-regulates prostacyclin synthease protein expression and inhibits endothelial cell apoptosis Eur J Pharmacol 2007, 554: 1-7
  30. 30. 武源,郭宏宝,王铁军,王银叶. 几种中药组分对家兔体外血小板聚集作用的比较. 中国临床药理学与治疗学2007;12(9):1047-1051
  31. 31. Wu XL, Wang YY, Cheng J, Zhao YY. Calcium channel blocking activity of calycosin, a major active component of Astragali Radix, on rat aorta. Acta Pharmacol Sin.2006; 27 (8): 1007-1012
  32. 32. Hu He,Tang Zhiyu,ChenShizhon,Wang Yinye*,Honokiol ameliorates focal cerebral ischemia and enhance tissue reactive oxygen species scavenging capacity after cerebral ischemial-reperfusion. Chin J Pharmacol Toxic 2006; 20: 455-460
  33. 33. Liu Xiaoyan,,Li Fengyun, Chi Zhihong, Wang Yinye*. Protective effect of oral fructose-1,6-diphosphate on liver injury in animal model. J Chin Pharmaceut Sci 2006; 15(3): 188-193
  34. 34. 胡蝶, 郭宏宝, 郭绪林, 王银叶. 单用和复方中硝酸异山梨酯的药动学比较研究. 中国药学杂志2006;12(4):24
  35. 35. Hu H, Zhang XX, Wang YY*, Chen SZ. Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacologica Sinica 2005; 26(9)1063-1068.
  36. 36. 王银叶,张晓雪,刘晓岩,李洁璇. 重组犬钩虫抗凝肽突变体及其载体、核苷酸序列、其制备和用途. ZL200610065641.0(专利)