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

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

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8mg/kg),恩度组2(造模后24h开始给予恩度8mg/kg),联合组(顺铂1mg/kg+恩度8mg/kg),顺铂组(顺铂1mg/kg),恩度组2从造模后24h开始给药,其余各组从第6天开始给药,顺铂5d,恩度6d,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。

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.