重组人血管内皮抑素间插联合顺铂对H22小鼠腹水瘤抑制作用的研究  

Research on intercalated combination of recombinant human endostatin and cisplatin in H22 tumor ascite model

作　　者：魏红梅 秦叔逵[2] 殷晓进 陈亚利 华海清[2] 王琳[2] 杨宁蓉[2] 陈映霞[2] 刘秀峰[2] 

机构地区：[1]山东青岛青岛市中心医院肿瘤综合治疗科,266042 [2]解放军八一医院全军肿瘤中心肿瘤内科,210002 [3]江苏先声药物有限公司研究院,210042

出　　处：《临床肿瘤学杂志》2014年第2期122-127,共6页Chinese Clinical Oncology

基　　金：中国博士后科学基金面上资助项目(20090451574);江苏省博士后基金资助项目(820901063C)

摘　　要：目的观察重组人血管内皮抑制素(恩度)间插联合顺铂腹腔内注射治疗小鼠腹水瘤的疗效和安全性。方法采用肝细胞癌H22腹水瘤细胞株建立小鼠腹水瘤模型。120只造模后的ICR小鼠随机分为4组:对照组(生理盐水d1~d10)、恩度组(恩度8mg/kg,d1~d5,d7~d10,生理盐水d6)、顺铂组(顺铂0.04mg/kg,d6,生理盐水d1~d5,d7~d10)及恩度联合顺铂组(恩度8mg/kg,d1~d5,d7~d10;顺铂0.04mg/kg,d6),每组30只,每只小鼠腹腔注射的药物体积均为0.2ml。记录各组小鼠腹水体积、腹水中肿瘤细胞、红细胞计数以及生存期;观察各组荷瘤小鼠腹膜和腹腔脏器种植转移情况;检测各组小鼠的腹膜渗透性、血常规和肝肾功能;流式细胞仪检测各组小鼠腹腔积液中肿瘤细胞凋亡情况。结果与对照组相比,恩度组和顺铂组和恩度联合顺铂组均能减少荷瘤小鼠腹腔积液的体积、肿瘤细胞数和红细胞数,延长荷瘤小鼠的生存时间。在上述指标中,恩度联合顺铂组与恩度组和顺铂组比较,差异有统计学意义(P<0.05)。恩度联合顺铂组小鼠腹腔积液中肿瘤细胞的凋亡率显著高于恩度组和对照组(P<0.05),但与顺铂组比较差异无统计学意义(P>0.05);恩度联合顺铂组小鼠的腹膜渗透性明显低于顺铂组和对照组(P<0.05),但恩度联合顺铂组与恩度组比较差异无统计学意义(P>0.05)。恩度联合顺铂组小鼠的体重增加及腹腔种植转移均少于其他3组。各组小鼠均未出现血常规和肝肾功能明显异常。结论恩度间插联合顺铂腹腔内应用治疗小鼠H22腹水瘤疗效显著,安全性好。Objective To observe the effects and safety of intercalated combination of recombinant human endostatin （en- dostar） and cisplatin by intraperitoneal injection in mice model bearing tumor ascite. Methods The tumor ascites model were estab- lished with hepatocellular carcinoma H22 cell lines by intraperitoneal injection. One hundred and twenty ICR mice were randomly as- signed into 4 groups： control group（ normal saline d^-d^o） , endostar group（endostar 8mg/kg, d1-d5, d7-d10 ; normal saline d6 ）, cispl- atin group（ cisplatin 0. 04mg/kg, d6 ; normal saline dl-dS, dT-dl0 ） and combined group （ endostar 8mg/kg, d1-d5, d7-dl0 ; cisplatin 0. 04mg/kg,d6 ）. Body weight, volume of ascites, the number of tumor ceils and red cells were measured. The peritoneum permeability assay, blood routine, liver function and renal function were tested in each group respectively. Implantation metastasis of tumor was ob- served in abdominal cavity of mice. Apoptosis of tumor cells in the ascites fluid were detected by flow cytometry. Survival time of each mouse was recorded. Results Compared with the control group, endostar group, cisplatin group and combined group could inhibit as- cites accumulation, reduce the counts of tumor cells and red cells in the ascites fluid and tumor burden of abdominal cavity, as well as prolonging survival of mice （P〈0. 05）. In those above items, combined group showed statistic significance compared with endostar group and cisplatin group（P〈0. 05）. Combined group significantly increased apoptosis of tumor cells compared with control group and endostar group （P 〈 0. 05 ）, but showed no difference with cisplatin grouo （P 〉 0. 05 ）. Combined ~roup obviously inhibited theperitoneum permeability compared with control group and cisplatin group（ P〈0. 05 ）, but showed no difference with endostar group（ P〉 0. 05）. Peritoneal metastasis and weight gain were less in combined group compared with the other 3 groups. Blood routine, liver func- tion and renal funct

关 键 词：重组人血管内皮抑素 顺铂 腹水瘤 腹膜渗透性 凋亡 

分 类 号：R73-36[医药卫生—肿瘤]