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中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (7): 752-755.

• 研究原著 • 上一篇    下一篇

地塞米松当归多糖前体药对三硝基苯磺酸诱导的大鼠溃疡性结肠炎的治疗作用

刘新友, 周四元, 程建峰1, 滕增辉, 冉玉华, 杨润涛, 杨茜, 梅其炳   

  1. 1第四军医大学药学系药理学教研室, 西安 710032, 陕西;
    2第四军医大学唐都医院药剂科, 西安 710038, 陕西
  • 收稿日期:2006-04-17 修回日期:2006-06-30 出版日期:2006-07-26 发布日期:2020-10-30
  • 通讯作者: 梅其炳,男, 教授, 博士生导师, 研究方向:分子药理学。Tel:029-84774552 E-mail:qbmei@fmmu.edu.cn
  • 作者简介:刘新友, 男, 硕士, 主管药师, 研究方向:药代动力学。Tel:029-84774555 E-mail:lxylxywy@163.com
  • 基金资助:
    国家“ 863” 计划资助项目(No2004AA2Z3160)

Effect of dexamethasone Angelica sinensis polysaccharide prodrug on trinitrobenzene sulfonic acid induced ulcerative colitis in rats

LIU Xin-you, ZHOU Si-yuan, CHENG Jian-feng1, TENG Zeng-hui, RAN Yu-hua, YANG Run-tao,YANG Xi, MEI Qi-bing   

  1. 1National Beijing Center for Drug Safety Evaluation and Research ,Beijing Institute of Pharmacology and Toxicology , Beijing 100850 , China
  • Received:2006-04-17 Revised:2006-06-30 Online:2006-07-26 Published:2020-10-30

摘要: 目的 探讨地塞米松当归多糖前体药(dexamethasone Angelica sinensis polysaccharide prodrug, DEXAP)对三硝基苯磺酸(TNBS) 诱导的溃疡性结肠炎(ulcerative colitis, UC) 的治疗作用及副作用。方法 :采用TNBS 的45 %乙醇溶液(50 mg·ml-1 ) 灌肠诱导实验性UC 大鼠模型, 分别采用0.25 μmol·kg-1·d-1地塞米松(DEX) 及0.05 、0.25 、1.25 μmol·kg-1·d-1DEX-AP(以地塞米松含量计) 灌胃治疗7 d 。检测外周血淋巴细胞数后处死动物, 取肾脏、脾脏和结肠称重。计算结肠溃疡面积后, 取部分结肠粘膜组织测髓过氧化物酶(myeloperoxidase,MPO) 活性, 部分结肠组织制作石蜡切片, HE 染色后进行光镜观察。结果 :TNBS 诱导的UC 大鼠经0.05 、0.25 、1.25 μmol·kg-1·d-1DEX-AP 治疗7 d 后, 与模型组比较, DEX 组结肠重量未见明显变化, 而DEX-AP 各组结肠重量均明显降低(P<0.05);DEX 组与DEXAP各组的结肠组织MPO 酶活性均显著降低, 且DEX-AP 降低MPO 酶活性具有剂量依赖性。0.25 μmol·kg-1·d-1 DEX 使UC 大鼠外周血淋巴细胞数、胸腺及脾脏重量均显著降低(P<0.01);0.05 、0.25 μmol·kg-1 ·d-1DEX-AP 对UC 大鼠外周血淋巴细胞数、胸腺及脾脏重量未见明显影响(P>0.05);1.25 μmol·kg-1·d-1 DEX-AP 对脾脏重量未见明显影响, 却使胸腺重量及外周血淋巴细胞数降低, 但仍显著高于0.25 μmol·kg-1 ·d-1 DEX 组(P<0.01) 。UC 大鼠经1.25 μmol·kg-1·d-1 DEX-AP 治疗后, 结肠粘膜组织结构基本恢复正常。结论 :DEX-AP 对TNBS 诱导的实验性UC 大鼠具有显著的治疗作用, 且副作用低, 具有良好的应用前景。

关键词: 溃疡性结肠炎, 三硝基苯磺酸, 地塞米松前体药, 当归多糖

Abstract: AIM: To explore the therapeutic effect of dexamethasone Angelica sinensis polysaccharide prodrug(DEX-AP) on trinitrobenzene sulfonic acid (TNBS) induced ulcerative colitis (UC) in rats and its side effects.METHODS: The experimental UC rats were induced by clusis of the solution of TNBS in 45 % alcoho1 (50 mg·ml-1 ).The UC rats were orally administrated with0.25μmol·kg-1·d-1 DEX and 0.05, 0.25, 1.25μmol·kg-1 ·d-1 DEX-AP (calculated by carried DEX in DEX-AP) for 7 days, respectively.The rats were killed after the amount of peripheral blood lymphocyte was counted,then the spleen, thymus and colon were separated and weighted.After the ulcerative area of colon was calculated,the colonic myeloperoxidase (MPO) activity was determined and parts of colon were paraffin sectioned and examined under light microscope by HE stain.RESULTS: After the UC rats were administrated with different doses of DEX-AP for 7 days, the ulcerative area, the weight and the MPO activity of colon reduced significantly.The reduction of MPO activity was correlated to the dose of DEX-AP and the MPO activity with DEX-AP at the doses of 0.25, 1.25μmol·kg-1 ·d-1 reduced more significantly than that with DEX at the the dose of 0.25μmol·kg-1·d-1.The number of peripheral blood lymphocyte,spleen weight and thymus weight of UC rats reduced significantly at the dose of 0.25μmol·kg-1 ·d-1DEX (P<0.01, compared with control group).DEXAP showed no significant effect on the number of peripheral blood lymphocyte, spleen weight and thymus weight of UC rats at the doses of 0.05, 0.25 μmol·kg-1 ·d-1.With the administration of 1.25 μmol·kg-1·d-1 DEX-AP to UC rats, the structure of the colonic mucosal tissue almost recovered.CONCLUSION: DEX-AP has significant therapeutic effect on TNBS induced UC rats and it has no obvious side effects, thus it indicates a great potential in treating UC.

Key words: bladder cancer, adriamycin, polyvinylpyrrolidone, apoptosis

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