重组人内抑素对佐剂性关节炎大鼠滑膜组织血管内皮细胞生长因子表达的影响

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (7): 760-763.

重组人内抑素对佐剂性关节炎大鼠滑膜组织血管内皮细胞生长因子表达的影响

夏丽娟, 陈飞虎, 黄学应, 刘永靖, 李俊

安徽医科大学药学院, 合肥 230032, 安徽

收稿日期:2006-04-14 修回日期:2006-05-08 出版日期:2006-07-26 发布日期:2020-10-30
通讯作者: 陈飞虎, ,男, 博士, 教授、博士生导师, 主要从事抗炎免疫药理学研究及分子药理学研究。Tel:0551-5161116 E-mail:cfhchina@sohu.com
作者简介:夏丽娟, 女, 硕士研究生, 研究方向:抗炎免疫药理学。Tel:0551-5161115 E-mail:xljahmu@sohu.com
基金资助:
国家自然科学基金资助项目(No30572196)

Effect of recombinant human endostatin on expression of vascular endothelial cell growth factor in adjuvant arthritis synovium tissue

XIA Li-juan, CHEN Fei-hu, HUANG Xue-ying, LIU Yong-jing, LI Jun

College of Pharmacy , Anhui Medical University, Hefei 230032 , Anhui, China

Received:2006-04-14 Revised:2006-05-08 Online:2006-07-26 Published:2020-10-30

摘要/Abstract

摘要： 目的观察重组人内抑素对佐剂性关节炎大鼠滑膜组织血管内皮细胞生长因子(vascular endothelial cell growth factor, VEGF) 的表达及其作用。方法采用弗氏完全佐剂(Freund' s complete adjuvant,CFA) 诱导的佐剂性关节炎(adjuvant-induced arthritis,AA) 大鼠模型, 用足容积法测量关节肿胀度;免疫组织化学法检测血管内皮细胞生长因子的表达及其对微血管密度的影响。结果弗氏完全佐剂致炎后d 10, 佐剂性关节炎大鼠出现继发性炎症, 皮下注射给予不同剂量的重组人内抑素(1.25 、2.5 、5 mg·kg^-1 ) , 连续7 d, 对照组于d 10 给予氨甲喋呤(Methotrexate,MTX, 1.0 mg·kg^-1 ) 。重组人内抑素各剂量组能明显抑制AA 大鼠的继发性足肿胀, 重组人内抑素各剂量组可不同程度减少AA 大鼠关节滑膜组织高表达的VEGF, 还可使滑膜组织的微血管密度减少。结论重组人内抑素可显著抑制AA 大鼠滑膜组织VEGF 的表达及微血管密度, 该作用可能与抑制血管翳的生成及减少滑膜细胞表面VEGF的表达有关。

关键词: 重组人内抑素, 佐剂性关节炎, 血管内皮细胞生长因子, 微血管密度

Abstract: AIM: To investigate the effect of recombinant human endostatin on the expression of vascular endothelial cell growth factor (VEGF) in adjuvant arthritis synovium tissue.METHODS: Adjuvant arthritis rat model was induced by a single intradermal injection of 100 μl of Freund' s complete adjuvant(CFA) on d 0.The volume of rat hind paw was measured by means of Volume Meter.The expression of VEGF and microvessel density of the synovial tissue were measured by immunohistochemical method.RESULTS: The secondary inflammation of Adjuvant-induced arthritis(AA) rats appeared on the d 10 after the injection of CFA.The therapeutic administration of recombinant human endostatin(1.25, 2.5, 5.0 mg·kg^-1 )were given for 7 days consecutively.Methotrexate (MTX)(1.0 mg·kg^-1 )was given only once on d 10 as the control.It was found that recombinant human endostatin significantly inhibited the secondary paw swelling.Recombinant human endostatin significantly decreased the expression of VEGF and microvessel density of the synovial tissue on AA rats.CONCLUSION: Recombinant human endostatin had an inhibitory effect on the expression of VEGF and microvessel density of the synovial tissue on AA rats, which was related to its anti-angiogenesis and an inhibition of VEGF on synoviocytes.

Key words: recombinant human endostatin, adjuvantarthritis, vascular endothelial cell growth factor, microvessel density

中图分类号:

R965
R966

夏丽娟, 陈飞虎, 黄学应, 刘永靖, 李俊. 重组人内抑素对佐剂性关节炎大鼠滑膜组织血管内皮细胞生长因子表达的影响[J]. 中国临床药理学与治疗学, 2006, 11(7): 760-763.

XIA Li-juan, CHEN Fei-hu, HUANG Xue-ying, LIU Yong-jing, LI Jun. Effect of recombinant human endostatin on expression of vascular endothelial cell growth factor in adjuvant arthritis synovium tissue[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(7): 760-763.

参考文献

1 Taylor PC.VEGF and imaging of vessels in rheumatoid arthritis[J].Arthritis Res, 200;4:S99-107
2 O' Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS,et al.Endostatin:an endogenous inhibitor of angiogenesis and tumor growth[J].Cell, 199;88:277-85
3 Fenton BM, Paoni SF, Beauchamp BK, Tran B, Liang L, Grimwood B, et al.Evaluation of microregional variations in tumor hypoxia following the administration of endostatin[J].Adv Exp Med Biol, 2003;5:19-24
4 Ponnazhagan S, Mahendra G, Kumar S, Shaw DR, Stockard CR,Grizzle WE, et al.Adeno-associated virus 2-mediated antiangiogenic cancer gene therapy:long-term efficacy of a vector encoding angiostatin and endostatin over vectors encoding a single factor[J].Cancer Res, 2004;6:1781-7
5 Nap AW, Griffioen AW, Dunselman GA, Bouma-Ter Steege JC,Thijssen VL, Evers JL, et al.Antiangiogenesis Therapy for Endometriosis[J].J Clin Endocrinol Metab, 200;89:1089-95
6 岳莉, 沈玉先, 王华, 郑咏秋, 魏伟, 徐淑云, 等.重组人内抑素对大鼠佐剂性关节炎继发性炎症的抑制作用[J].中国药理学通报, 2003;1:899-902
7 徐叔云, 卞如濂, 陈修.药理实验方法学[ M].第版.北京:人民卫生出版社, 1991:723-4
8 Friestein GS.Invasive fibroblast-like synoviocytes in rheumatoid arthritis:passive responders or transformed aggressors[J].Arthritis Rheum, 199;39:1781-90
9 Mulherin D, Fitzgerald O, Bresnihan B.Synovial tissue macrophage populations and articular damage in rheumatoid arthritis[J].Arthritis Rheum, 1996;39:115-24
10 Ferrara N, Henzel WJ.Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells[J].Biochem Biophys Res Commun, 198;161:851-8
11 Roccaro AM, Russo F, Cirulli T, Pieto GD, Vacca A, Dammacco F.Antiangiogenesis for Rheumatoid Arthritis[J].Curr Drug Targets Inflamm Allergy, 2005;4:27-30
12 Paleolog EM.Angiogenesis in rheumatoid arthritis[J].Arthritis Res, 2002;4:S81-90
13 陈飞虎.肿瘤血管生成抑制因子及Endostatin 研究进展[J].安徽医药, 200;7:5-7
14 Chavakis E, Dimmeler S.Regulation of endothelial cell survival and apoptosis during angiogenesis[J].Arterioscler Thromb Vasc Biol, 2002;2:887-93
15 Hamano Y, Sugimoto H, Soubasakos MA, Kieran M, Olsen BR,Lawler J, et al.Thrombospondin-associated with tumor microenvironment contributes to low-dose cyclophosphamide-mediated endothelial cell apoptosis and tumor growth suppression[J].Cancer Res, 2004;6:1570-4

[1]	刘红丹，殷一红. 麒麟丸预防体外受精胚胎移植术后所致卵巢过度刺激综合征患者的疗效及对血浆相关指标的影响[J]. 中国临床药理学与治疗学, 2020, 25(2): 196-202.
[2]	程润，丁文溪，严尚学，魏伟. 人脐带来源间充质干细胞对佐剂性关节炎大鼠巨噬细胞功能的影响[J]. 中国临床药理学与治疗学, 2019, 24(12): 1335-1340.
[3]	夏丽娟，何云芹，邵明君. 左炔诺孕酮宫内节育系统治疗无排卵型功能失调性子宫出血的疗效[J]. 中国临床药理学与治疗学, 2017, 22(6): 699-704.
[4]	钟永翔, 林晓, 王恩智, 王鑫华. 三氧化二砷、VEGF对人骨肉瘤Saos-2细胞TRAF-2和STAT-6表达的影响[J]. 中国临床药理学与治疗学, 2015, 20(9): 993-997.
[5]	徐晓芳, 张蕾蕾, 贾仁兵, 周一雄, 宋欣, 范先群. 睑板腺癌中MMP-2的表达及其临床意义[J]. 中国临床药理学与治疗学, 2015, 20(5): 557-561.
[6]	张海岩, 李婷婷, 范慢利, 吕心蕊, 苏宇, 张骏艳, 周兰兰. 芩柏复方烫伤膏对大鼠实验性烫伤模型的保护作用[J]. 中国临床药理学与治疗学, 2015, 20(4): 399-403.
[7]	王升晔, 杜向慧. 贝伐单抗在乳腺癌治疗中的疗效和风险评估[J]. 中国临床药理学与治疗学, 2013, 18(1): 115-120.
[8]	曾阳, 马继雄, 鲍敏, 陈海娟, 张国燕, 张洪泉. 藏药翁布总苷对大鼠佐剂性关节炎的治疗作用[J]. 中国临床药理学与治疗学, 2010, 15(12): 1321-1325.
[9]	张腾跃, 陈飞虎, 王念, 袁凤来, 胡伟, 吴繁荣. 酸敏感离子通道阻断剂阿米洛利对佐剂性关节炎大鼠关节软骨细胞凋亡抑制作用的初步研究[J]. 中国临床药理学与治疗学, 2010, 15(1): 41-46.
[10]	陈飞虎, 袁凤来, 李霞, 吴繁荣, 黄学应, 胡伟, 沈娟, 李俊. 几种抗类风湿性关节炎药物对佐剂性关节炎大鼠关节软骨细胞酸敏感离子通道的表达影响及作用[J]. 中国临床药理学与治疗学, 2008, 13(2): 131-137.
[11]	黄学应, 陈飞虎, 刘永靖, 张晓明, 袁凤未. 重组人内抑素对佐剂性关节炎大鼠滑膜组织凋亡相关基因表达的影响[J]. 中国临床药理学与治疗学, 2007, 12(12): 1359-1363.
[12]	邴飞虹, 张国斌, 邓成志, 苏彦奇. 木瓜丸对大鼠佐剂性关节炎的防治作用[J]. 中国临床药理学与治疗学, 2006, 11(5): 590-592.
[13]	卢延旭, 陈敏珠, 路景涛. IL-10 与可溶性鸡Ⅱ型胶原对实验性关节炎的联合治疗作用[J]. 中国临床药理学与治疗学, 2004, 9(4): 426-429.
[14]	方伟蓉, 李运曼, 钟林霖. 苦杏仁苷对佐剂性炎症影响的实验研究[J]. 中国临床药理学与治疗学, 2004, 9(3): 289-293.
[15]	武健, 李先海, 夏祥厚, 王亚兵, 阎竟一. 生长抑素及类似物对大肠癌组织血管生成的调控[J]. 中国临床药理学与治疗学, 2004, 9(3): 333-336.