西安交通大学学报（医学版）2016，Vol.37Issue(3)：378-382,398,6.DOI:10.7652/jdyxb201603016
Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
Sorafenib ameliorates renal fibrosis through inhibition of TGF-β/Smad pathway
摘要
Abstract
Objective To investigate the effect of sorafenib in ameliorating renal fibrosis and its possible mechanisms.Methods Rats were subjected to unilateral ureteral obstruction (UUO ) and intragastrically administered sorafenib.NRK-52E cells were treated with transforming growth factor-β1 (TGF-β1)and sorafenib. HE staining was used to visualize renal fibrosis.α-SMA and E-cadherin expressions in kidney tissue and NRK-52E cells were performed using immunofluorescence.The cell cycle of NRK-52E cells was determined by flow cytometry analysis.Smad3 and p-Smad3 protein expressions in NRK-52E cells were detected by Western blot analysis. Results HE staining showed that kidney interstitial fibrosis,tubular atrophy,and inflammatory cell infiltration in the sorafenib-treated UUO groups were significantly decreased compared with the vehicle-treated UUO group (P<0.05).Compared with those in UUO and TGF-β-stimulated NRK-52E groups,the expression of a-SMA decreased but E-cadherin expression increased in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (P<0.05).After 24 h stimulation with TGF-β1 5 ng/mL,the number of cell cycles arrested in G0/G1 phase was significantly increased and the number of cells that entered G2 ,S phase decreased (P<0 .0 5 ).Compared with that in TGF-β-stimulated NRK-52E groups, p-Smad3 decreased in the sorafenib-treated groups (P<0.05). Conclusion Our results suggest that sorafenib may be useful for the treatment of renal fibrosis through suppressing TGF-β/Smad3 signaling.关键词
索拉菲尼(sorafenib)/肾纤维化/间质上皮细胞转分化/TGF-β/Smad3Key words
sorafenib/renal fibrosis/epithelial-mesenchymal transition (EMT)/transforming growth factor-β(TGF-β)/Smad3分类
医药卫生引用本文复制引用
贾利宁,马晓桃,杨阳,付荣国,桂保松..Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究[J].西安交通大学学报（医学版）,2016,37(3):378-382,398,6.基金项目
陕西省自然科学基金资助项目(No.2015JM8429) Supported by the Natural Science Foundation of Shaanxi Province (No.2015JM8429) （No.2015JM8429）
