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中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (5): 507-511.

• 基础研究 • 上一篇    下一篇

重组人血管内皮抑素治疗小鼠恶性腹腔积液疗效及作用机制研究

吴春艳1, 王伟1, 陈鑫1, 陈冬云2, 芮景3   

  1. 1皖南医学院,芜湖 241000,安徽;
    2皖南医学院第一附属医院弋矶山医院肿瘤内科;
    3普外科,芜湖 241000,安徽
  • 收稿日期:2014-01-13 修回日期:2014-05-08 出版日期:2014-05-26 发布日期:2014-06-05
  • 通讯作者: 芮景,男,教授,主任医师,研究生导师,研究方向:蛇毒抗肿瘤的基础与临床。E-mail: ruijing1956@sina.com
  • 作者简介:吴春艳,女,在读研究生,研究方向:蛇毒抗肿瘤的基础与临床。Tel: 15155338486 E-mail: yanyujiangnan212@sina.com

Efficacy and therapeutic mechanism of recombinant human endostatin on malignant ascites in mice

WU Chun-yan1, WANG Wei1, CHEN Xin1, CHEN Dong-yun2, RUI Jing3   

  1. 1Wannan Medical College, Wuhu 241000, Anhui, China;
    2Department of Medical Oncology;
    3Genereal Surgey Department, Affiliated Yijishan Hospital of Wannan Medical College ,Wuhu 241000,Anhui, China
  • Received:2014-01-13 Revised:2014-05-08 Online:2014-05-26 Published:2014-06-05

摘要: 目的:研究重组人血管内皮抑素(恩度)治疗小鼠恶性腹腔积液的疗效及作用机制。方法:用小鼠H22细胞系建立小鼠恶性腹水瘤模型。120只ICR小鼠随机分为5组:对照组(0.9%NS),恩度组1(恩度 8 mg/kg),恩度组2(造模后 24 h 开始给予恩度 8 mg/kg),联合组(顺铂 1 mg/kg+恩度 8 mg/kg),顺铂组(顺铂 1 mg/kg),恩度组2从造模后 24 h 开始给药,其余各组从第6天开始给药,顺铂 5 d,恩度 6 d,均为1次/d。记录各组小鼠体重、腹水体积、生存期和明显不良反应;测定小鼠腹水伊文思蓝的吸光度值间接反映小鼠腹膜通透性;采用ELISA法测定小鼠血清、腹水中血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)浓度。结果:与对照组比较,各实验组均能抑制小鼠腹水生成、延长小鼠生存期,降低小鼠腹膜通透性及小鼠血清、腹水中VEGF、MMP-2水平(P<0.05),以联合组较明显。结论:恩度联合顺铂治疗小鼠恶性腹腔积液疗效优于恩度、顺铂单药,其作用机制可能为联合用药进一步降低了小鼠血清、腹水中VEGF、MMP-2水平。

关键词: 重组人血管内皮抑素, 顺铂, H22细胞腹水瘤, VEGF, MMP-2

Abstract: AIM: To investigate the effect and mechanism of recombinant human endostatin (endostar) in therapy malignant ascites in mice.METHODS: Mouse models bearing ascites tumors were established via intraperitoneal injection of H22 cell lines.120 ICR mice were randomly divided into 5 groups and recieved intraperitoneal injection once a day for five(cisplatin)or six(endoustar) days: control(0.9% normal saline),endostar group1(8 mg/kg), endostar group2 (8 mg/kg, received injection after H22 cell line injection 24 hours),combined group (endostar 8 mg/kg plus cisplatin 1 mg/kg), cisplatin group (1 mg/kg). Besides the endostar group2, all groups received intraperitoneal injection at the sixth day after mouse model established .Weight, volume of ascites ,life span and adverse reaction in each group were recorded respectively.The levels of Evan's blue dye in the ascites fluid were assayed to determine the mouse peritoneal microvascular permeability.The levels of VEGF, MMP-2 in serum and ascites fluid were determined by ELISA assay.RESULTS: Compared with control group, all treatment groups could reduce the peritoneal ascites fluid,prolong the life span, decrease the peritoneal microvascular permeability and levels of VEGF, MMP-2 in serum and ascites fluid (P<0.05),and the combined group is more obviously.CONCLUSION: Endostar combined with cisplatin could improve the efficacy because it significantly decreases the levels of VEGF, MMP-2 in serum and ascites fluid.

Key words: recombinant human endostatin, cisplatin, H22 cell ascites tumor, vascular endothelial growth factor(VEGF), matrix metalloproteinase-2(MMP-2)

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