You Qi, Kong Ling-Jian, Li Feng-Dong, Wang Hang-Yu, Liu Dian-Gang, Pei Feng-Hua, Song Ji-Tao, Xu Jun, Chen Jing
Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150080, P.R. China.
Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Mol Med Rep. 2015 Oct;12(4):5594-600. doi: 10.3892/mmr.2015.4103. Epub 2015 Jul 20.
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.
本研究的目的是检测重组人内皮抑素恩度对四氯化碳诱导的小鼠肝纤维化模型中肝血窦毛细血管化的影响。通过腹腔注射四氯化碳6周，在BALB/c小鼠中诱导肝纤维化模型。将动物分为以下六个治疗组：第1组，正常动物；第2组，四氯化碳诱导的肝纤维化；第3组，四氯化碳+恩度20mg/kg/天，共6周；第4组，四氯化碳+恩度10mg/kg/天，共6周；第5组，四氯化碳+恩度20mg/kg/天，共4周；第6组，四氯化碳+恩度10mg/kg/天，共4周。使用透射电子显微镜测定每个肝血窦的窗孔平均数量。通过蛋白质免疫印迹分析检测血管内皮生长因子（VEGF）及其受体（VEGFR）1和2的表达。正常对照组和未治疗的模型纤维化小鼠之间，以及未治疗的模型和恩度治疗的小鼠之间，每个血窦的窗孔数量存在显著差异（P<0.01和P<0.05）。恩度治疗与肝组织中VEGFR1和VEGFR2水平降低相关（P<0.01），并且与四氯化碳诱导的小鼠肝纤维化模型中肝血窦内皮细胞毛细血管化减少相关，这种作用可能涉及VEGF途径。然而，需要进一步研究来证实其在其他肝纤维化病因中的作用。
