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

BMC Gastroenterology

Xiaorong Chen¹  Qingnian Xu¹  Hui Miao¹  Bozong Tang¹  Yunfei Lu¹  Lei Wang²  Zongguo Yang¹  Cheng Liu³ 

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

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

Others  :  1234285
DOI  :  10.1186/s12876-015-0380-5

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

【 摘 要 】

Background/aims

Liver 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.

Methods

Liver 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.

Results

The 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.

Conclusion

Sorafenib 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】

   
2015 Liu et al.

【 图 表 】

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