机构：[1]Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China[2]Department of General Surgery, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China普通外科首都医科大学宣武医院[3]Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, China[4]Department of Gastroenterology, the First Hospital of Harbin, Harbin, Heilongjiang 150010, China
Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, a-smooth muscle actin (alpha-SMA), TGF-beta 1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, alpha-SMA, and TGF-beta 1 were measured by real-time PCR. Collagen I and transforming growth factor beta 1 (TGF-beta 1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P<0.05). Moreover, Endostar inhibited the hepatic expression of alpha-SMA, TGF-beta 1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P<0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of alpha-SMA, Collagen-1, and TGF-beta 1 mRNA. Expressions of Collagen-1 and TGF-beta 1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P<0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.
基金：
the Education Fund of Heilongjiang Province (No. 12511287).
第一作者机构：[1]Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China
共同第一作者：
通讯作者：
通讯机构：[3]Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, China
推荐引用方式(GB/T 7714)：
Jing Chen,Dian-Gang Liu,Guang Yang,et al.Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice[J].EXPERIMENTAL BIOLOGY AND MEDICINE.2014,239(8):998-1006.doi:10.1177/1535370214532595.
APA：
Jing Chen,Dian-Gang Liu,Guang Yang,Ling-Jian Kong,Ya-Ju Du...&Bao-Xin Li.(2014).Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.EXPERIMENTAL BIOLOGY AND MEDICINE,239,(8)
MLA：
Jing Chen,et al."Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice".EXPERIMENTAL BIOLOGY AND MEDICINE 239..8(2014):998-1006
