CAJ | 학술논문

目的观察重组人血管内皮抑素(Endostar,YH-16)对小鼠恶性腹腔积液及血清中血管内皮生长因子(VEGF)表达的影响,初步探讨其抑制恶性胸腹腔积液形成的机制.方法 H22肝癌细胞系接种BALB/C小鼠腹腔建立腹水瘤模型,随机分为:Ⅰ组:阴性对照组；Ⅱ组:顺铂组；Ⅲ～Ⅴ组:低、中和高剂量Endostar组；Ⅵ组:Endostar与顺铂联合组.实验药物腹腔注射,记录小鼠体质量作为计量腹水变化指标,观察生存期,检测腹水及血清中VEGF的表达.结果第9天Endostar各剂量组及顺铂组间小鼠体质量比较差异无统计学意义(P＞0.05),与对照组比较差异有统计学意义(P＜0.05),第11天Ⅳ组明显优于Ⅰ、Ⅱ、Ⅲ、Ⅴ组(P＜0.01),但较Ⅵ组差(P＜0.01)；Endostar不同剂量组小鼠的生存时间较Ⅰ组、Ⅱ组延长(P＜0.05),Ⅵ组中位生存时间最长(P＜0.05)；Endostar对小鼠恶性腹水及血清中VEGF的抑制作用:Ⅳ组下降较其他剂量组明显(P＜0.05),Ⅵ组优于单药各组,差异有统计学意义(P＜0.05).结论重组人血管内皮抑素可以通过下调荷瘤小鼠VEGF的表达从而抑制小鼠恶性腹腔积液的生成,延长荷瘤小鼠生存期；不同药物剂量以及中剂量联合顺铂均具有较好的治疗效果.
목적 관찰중조인혈관내피억소(Endostar,YH-16)대소서악성복강적액급혈청중혈관내피생장인자(VEGF)표체적영향,초보탐토기억제악성흉복강적액형성적궤제.방법 H22간암세포계접충BALB/C소서복강건립복수류모형,수궤분위:Ⅰ조:음성대조조；Ⅱ조:순박조；Ⅲ～Ⅴ조:저、중화고제량Endostar조；Ⅵ조:Endostar여순박연합조.실험약물복강주사,기록소서체질량작위계량복수변화지표,관찰생존기,검측복수급혈청중VEGF적표체.결과 제9천Endostar각제량조급순박조간소서체질량비교차이무통계학의의(P＞0.05),여대조조비교차이유통계학의의(P＜0.05),제11천Ⅳ조명현우우Ⅰ、Ⅱ、Ⅲ、Ⅴ조(P＜0.01),단교Ⅵ조차(P＜0.01)；Endostar불동제량조소서적생존시간교Ⅰ조、Ⅱ조연장(P＜0.05),Ⅵ조중위생존시간최장(P＜0.05)；Endostar대소서악성복수급혈청중VEGF적억제작용:Ⅳ조하강교기타제량조명현(P＜0.05),Ⅵ조우우단약각조,차이유통계학의의(P＜0.05).결론 중조인혈관내피억소가이통과하조하류소서VEGF적표체종이억제소서악성복강적액적생성,연장하류소서생존기；불동약물제량이급중제량연합순박균구유교호적치료효과.
Objective To observe the effect of recombinant human endostatin (Endostar,YH-16) on VEGF expression in malignant peritoneal effusion and serum of mice and its supressive mechanism on formation of malignant peritoneal effusion.Methods H22 hepatoma cell lines was inoculated into BALB/C mice to establish ascites tumor model.One hundred and eighty healthy BALB/C mice,after intraperitoneal inoculation,were randomly divided into six groups:group Ⅰ:saline negative control group; group Ⅱ:cisplatin positive control group; groups Ⅲ to Ⅴ:low,medium and high dose Endostar group; group Ⅵ:endostatin in combination with cisplatin group.When the peritoneal effusions grow,intraperitoneal injection of the experimental drug was given.The general condition of mice,the mice weight as ascites measurement indicators of change and the survival period was observed.The ascites and serum vascular endothelial growth factor (VEGF) expression was detected.Results Endostar inhibited the formation of malignant ascites in mice:on the 9th day,different doses of endostatin groups and group Ⅱ had no statistical differences in the weight of mice (P ＞ 0.05),but had statistal difference compared with group Ⅰ (P ＜ 0.05).The weight of mice of group Ⅳ on the 11 th day was better than that of group Ⅰ,Ⅱ,Ⅲ,Ⅴ (P ＜ 0.01),but it was worse than that in group Ⅵ (P ＜ 0.01).Endostatin on survival time of mice:the extended survival time of mice in group Ⅲ-Ⅴ were longer compared with group Ⅰ and Ⅱ,the differences were significant (P ＜ 0.05),and group Ⅵ had the longest median survival (P ＜ 0.05).Endostar inhibition mechanism for the formation of malignant ascites in mice:group Ⅳ retarded the ascites and serum VEGF better than that in group Ⅲ and Ⅴ (P ＜ 0.05),but the group Ⅵ had the best effect compared with other groups (P ＜ 0.05).Conclusions Recombinant human endostatin can inhibite the growth of malignant ascites in mice by reducing the expression of VEGF in tumor-bearing mice,also can extend the period of survival of tumor-bearing mice.Different dosage of endostar and middle-dosage of endostar combined with cisplatin have better treatment effect.