Combination of sorafenib and gadolinium chloride (GdCl3) attenuates dimethylnitrosamine(DMN)-induced liver fibrosis in rats

BMC Gastroenterology

Research Article

Lei Wang¹  Xiaorong Chen²  Qingnian Xu²  Zongguo Yang²  Yunfei Lu²  Hui Miao²  Bozong Tang²  Cheng Liu³ 

[1] Department of Hepatology, Affiliated hospital of Shandong University of Trasitional Chinese Medicine, 250014, Jinan, China;Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, 201508, Shanghai, China;Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, 201508, Shanghai, China;Laboratory of Molecular Pathology, Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200062, Shanghai, China;

关键词: Hepatic stellate cells;    Sinusoidal endothelial cells;    Kupffer cells;    Liver fibrosis;   

DOI  :  10.1186/s12876-015-0380-5

 received in 2015-01-19, accepted in 2015-10-19,  发布年份 2015

来源: Springer

【 摘 要 】

Background/aimsLiver sinusoidal endothelial cells (SECs), hepatic stellate cells (HSCs) and Kupffer cells (KCs) are involved in the development of liver fibrosis and represent a potential therapeutic target. The therapeutic effects on liver fibrosis of sorafenib, a multiple tyrosine kinase inhibitor, and gadolinium chloride (GdCl3), which depletes KCs, were evaluated in rats.MethodsLiver fibrosis was induced in rats with dimethylnitrosamine, and the effects of sorafenib and/or GdCl3 in these rats were monitored. Interactions among ECs, HSCs and KCs were assessed by laser confocal microscopy.ResultsThe combination of sorafenib and GdCl3, but not each agent alone, attenuated liver fibrosis and significantly reduced liver function and hydroxyproline (Hyp). Sorafenib significantly inhibited the expression of angiogenesis-associated cell markers and cytokines, including CD31, von Willebrand factor (vWF), and vascular endothelial growth factor, whereas GdCl3 suppressed macrophage-related cell markers and cytokines, including CD68, tumor necrosis factor-α, interleukin-1β, and CCL2. Laser confocal microscopy showed that sorafenib inhibited vWF expression and GdCl3 reduced CD68 staining. Sorafenib plus GdCl3 suppressed the interactions of HSCs, ECs and KCs.ConclusionSorafenib plus GdCl3 can suppress collagen accumulation, suggesting that this combination may be a potential therapeutic strategy in the treatment of liver fibrosis.

【 授权许可】

CC BY   
© Liu et al. 2015