腹腔内应用重组人血管内皮抑制素治疗艾氏腹水瘤的实验研究  

Research on administration of recombinant human endostatin by intraperitoneal iniection in ehrlich ascites carcinoma

作　　者：彭登付[1] 胡冰[1] 何义富[1] 陈健[1] 袁幸[1] 王伟[1] 李庆 

机构地区：[1]安徽医科大学附属省立医院中心实验室,合肥230001 [2]安徽医科大学附属省立医院肿瘤化疗科中心实验室,合肥230001

出　　处：《安徽医科大学学报》2014年第9期1218-1221,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省科技厅基金资助项目(编号:12070403084)

摘　　要：目的观察重组人血管内皮抑制素对艾氏腹水瘤(EAC)小鼠的治疗作用,并初步探讨其相关作用机制。方法采用四甲基偶氮唑蓝(MTT)法检测不同终浓度的重组人血管内皮抑制素(0、5、10、20、40μg/ml)对体外培养的EAC细胞的抑制率;利用EAC细胞建立腹水瘤小鼠模型,将54只腹水瘤小鼠随机分为3组:A组(重组人血管内皮抑制素8 mg/kg,每12 h腹腔注射1次)、B组(重组人血管内皮抑制素8 mg/kg,每24 h腹腔注射1次)、C组即对照组(生理盐水0.2 ml/只,每12 h腹腔注射1次)。详细记录小鼠腹水量、体重及生存期;酶联免疫吸附法(ELISA)检测小鼠腹水血管内皮生长因子(VEGF)及基质金属蛋白酶-2(MMP-2);并通过尾静脉注射伊文思蓝染液间接反映微血管通透性。结果体外实验显示,不同浓度的重组人血管内皮抑制素对EAC未见抑制作用;体内试验显示,重组人血管内皮抑制素组(A组和B组)小鼠的体重、腹水量及腹水中VEGF和MMP-2浓度均低于对照组,生存时间较对照组延长(P<0.05);3组小鼠血管通透性、A组与B组之间的各项指标差异无统计学意义(P>0.05)。结论腹腔内给药治疗小鼠EAC疗效较好,其作用机制可能与抑制VEGF及MMP-2的生成有关,提示重组人血管内皮抑制素在临床上治疗恶性腹水有较好的应用前景。Objective To observe the effect of recombinant human endostatin on ehrlich ascites carcinoma （EAC） mice and explore the underlying mechanism initially. Methods Developing EAC cells and the cells were treated with different concentrations of recombinant human endostatin （0, 5, 10, 20, 40）μg/ml for 24 h and then the growth inhibitory rate of each group cells was examined by MTT method. Mice with ascites models were established by intraperitoneal injection of ehrlich ascites carcinoma cells, and then 54 ICR mice were randomly divided into three groups： Group A （recombinant human endostatin 8 mg/kg, every 12 hours） , Group B （recombinant human endostatin 8 mg/kg, every 24 hours） and Group C （ NS 0.2 ml, every 24 hours）. Weight, ascites volume and sur- vival time were recorded and the concentration of vascular endothelial growth factor （VEGF） and matrix metallopro- teinase-2 （MMP-2） was measured by ELISA method respectively. Evans blue were injected via the caudal vein and then the peritoneal microvascular permeability was assessed indirectly. Results The weight, ascites volume and the concentration of VEGF and MMP-2 of Group A and Group B was lower than that of Group C （P 〈 0. 05 ）, while the survival time of recombinant human endostatin groups were longer than those of the Group C （ P 〈 0. 05 ）. How- ever, no statistical difference was found between Group A and Group B about the above indicators. Conclusion Recombinant human endostatin is an effective therapy for ehrlich ascites carcinoma mice and its mechanism may be associated with inhibition of the VEGF expression. Taken together, our preliminary findings suggest that recombi- nant human endostatin may have a favorable prospect in the clinical treatment of malignant ascites.

关 键 词：关键词重组人血管内皮抑制素 艾氏腹水瘤 血管内皮生长因子 基质金属蛋白酶-2 

分 类 号：R735[医药卫生—肿瘤] R739.9[医药卫生—临床医学]