重组人血管内皮抑素抑制沙鼠肝泡状棘球蚴周围血管生成的实验研究  

An animal study of inhibition of angiogenesis by Endostar in a gerbil model of hepatic alveolar echinococcosis

作　　者：陈骞[1,2] 张怀[1] 苏争鸣[1] 王岩[1] 张示杰[2] 

机构地区：[1]石河子大学医学院,新疆石河子832008 [2]石河子大学医学院第一附属医院肝胆外科

出　　处：《中国病原生物学杂志》2017年第4期321-324,327,共5页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.81560518)

摘　　要：目的探讨重组人血管内皮抑素恩度(endostar,YH-16)对沙鼠肝泡状棘球蚴(又称多房棘球蚴)组织周围血管生成的抑制作用。方法采用开腹肝穿刺法建立沙鼠肝泡球蚴动物模型,泡球蚴原头节混悬液接种量为0.1ml(约含原头节500个)。实验随机分为模型组(A组)、生理盐水组(B组)和重组人血管内皮抑素组(C组),10只/组。A组造模后不予任何干预,C组造模30d后开始给予恩度(10mg/kg)腹腔注射,1次/d,连用14d后停药7d,21d为一个疗程。B组腹腔注射等量生理盐水,方法同C组。用药3个疗程后解剖沙鼠,留取肝泡球蚴组织,采用免疫组化法和Western blot检测沙鼠肝泡状棘球蚴组织中血管内皮生长因子(VEGF)的表达及微血管密度(MVD-CD34)。结果 A、B、C组泡球蚴组织中VEGF评分分别为5.00±1.26、5.17±0.75、3.25±1.04,VEGF/β-肌动蛋白比值分别为1.11±0.06、1.10±0.07、0.63±0.10,C组VEGF表达水平与A、B组比较差异有统计学意义(P<0.05);MVD-CD34计数分别为9.20±1.02、8.76±1.34、4.55±1.09,CD34/β-肌动蛋白比值分别为1.10±0.10、1.13±0.07、0.77±0.12,C组微血管计数及CD34蛋白表达量与A、B组比较差异有统计学意义(P<0.05),A、B组相比VEGF和MVD-CD34表达水平差异无统计学意义(P>0.05)。结论恩度干预肝泡球蚴小鼠VEGF表达及微血管密度下降,表明重组人血管内皮抑素可抑制泡状棘球蚴周围血管生成。Objective To investigate the inhibition of angiogenesis by Endostar in a gerbil model of hepatic alveolar echinoeoceosis. Methods An alveolar Echinococcus sp. was injected into the abdominal cavity of 30 healthy gerbils to create an animal model of hepatic alveolar echinocoeeosis. Each gerbil was injected with 0.1 mL of a suspension of imma- ture protoscoleces of an alveolar Echinoeoecus sp. （containing about 500 protoseoleees）. The gerbils were then randomly divided into three groups of 10 animals each. One group served as the model （group A）, one group was administered sa- line （group B）, and one group was administered Endostar （group C）. Group A received no further treatment after injec- tion. Thirty days post--injection, Group C received an intraperitoneal injection of Endostar in 3 courses （each course las- ted 21 days： 10 mg/kg on day 1- 14 and respite for 7 days）. Group B received an intraperitoneal injection of a corre- sponding volume of saline in the same manner as group C. The gerbils were sacrificed once treatment was finished, and alveolar hydatid tissues were collected. Expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD--CD34） were evaluated with immunohistochemieal staining and Western blotting. Results VEGF was ex pressed as yellow or brown yellow granules located in the cytoplasm. The VEGF score was 5.00 ± 1.26 for group A, 5. 17 ±0.75 for group B, and 3.25 ± 1.04 for groupC. The VEGF/β--actin ratio was 1.11 ±0.06 for group A, 1.10 ± 0.07 for group β, and 0.63 ± 0.10 for group C. Immunohistochemistry and Western blotting revealed that the VEGF expression in group C was significantly inhibited compared to that in groups A and B （P〈0.05）. CD34--positive cells stained brown, and CD34 was mainly located in the cell membrane of endothelial cells. The CD34 score was 9.20 ± 1.02for group A, 8.76 ± 1.34 for group B, and 4.55 ±1.09 for group C. The CD34/-actin ratio was 1.10 ± 0. 10 for group A, 1.13±0.07 for group B, and 0

关 键 词：泡状棘球蚴 肝 血管生成抑制剂 内皮抑素类 血管内皮生长因子 微血管密度 

分 类 号：R383[医药卫生—医学寄生虫学]