CAJ | 학술논문

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。
목적관찰중조인혈관내피억제소대애씨복수류( EAC)소서적치료작용,병초보탐토기상관작용궤제。방법채용사갑기우담서람( MTT)법검측불동종농도적중조인혈관내피억제소(0、5、10、20、40μg /ml )대체외배양적EAC세포적억제솔；이용EAC세포건립복수류소서모형,장54지복수류소서수궤분위3조：A조(중조인혈관내피억제소8 mg/kg,매12 h복강주사1차)、B조(중조인혈관내피억제소8 mg/kg,매24 h복강주사1차)、C조즉대조조(생리염수0.2 ml/지,매12 h복강주사1차)。상세기록소서복수량、체중급생존기；매련면역흡부법( ELISA)검측소서복수혈관내피생장인자(VEGF)급기질금속단백매-2(MMP-2)；병통과미정맥주사이문사람염액간접반영미혈관통투성。결과체외실험현시,불동농도적중조인혈관내피억제소대EAC미견억제작용；체내시험현시,중조인혈관내피억제소조( A조화B조)소서적체중、복수량급복수중VEGF화MMP-2농도균저우대조조,생존시간교대조조연장( P <0.05)；3조소서혈관통투성、A조여B조지간적각항지표차이무통계학의의( P>0.05)。결론복강내급약치료소서EAC료효교호,기작용궤제가능여억제VEGF급MMP-2적생성유관,제시중조인혈관내피억제소재림상상치료악성복수유교호적응용전경。
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. ConclusionRecombinant 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.