Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4-induced fibrosis in mice

被引:15
作者
You, Qi [1 ]
Kong, Ling-Jian [2 ]
Li, Feng-Dong [2 ]
Wang, Hang-Yu [2 ]
Liu, Dian-Gang [3 ]
Pei, Feng-Hua [2 ]
Song, Ji-Tao [2 ]
Xu, Jun [2 ]
Chen, Jing [2 ]
机构
[1] Harbin Med Univ, Canc Hosp, Dept Gastrointestinal Surg, Harbin 150080, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Harbin 150086, Heilongjiang, Peoples R China
[3] Capital Med Univ, Xuanwu Hosp, Dept Gen Surg, Beijing 100053, Peoples R China
关键词
carbon tetrachloride; hepatic fibrosis; Endostar; endostatin; vascular endothelial growth factor; hepatic sinusoidal cell capillarization; CHRONIC LIVER-DISEASE; GROWTH-FACTOR; ANGIOGENESIS; SORAFENIB; MECHANISM;
D O I
10.3892/mmr.2015.4103
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4-induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4-induced liver fibrosis; group 3, CCl4-Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar-treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4-induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.
引用
收藏
页码:5594 / 5600
页数:7
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