中国药理学通报2017，Vol.33Issue(2)：212-217,218,7.DOI:10.3969/j.issn.1001-1978.2017.02.014
鞘氨醇激酶1在肾间质纤维化中的作用及机制研究
Role of SphK1 in renal tubulointerstitial fibrosis and its mechanism
摘要
Abstract
Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.关键词
鞘氨醇激酶 1/单侧输尿管结扎/自噬/纤维化/PF-543/电镜Key words
sphingosine kinase 1/unilateral ureteral obstruction/autophagy/fibrosis/PF-543/transmission e-lectron microscope分类
医药卫生引用本文复制引用
杜春阳,肖夏,王鑫贵,符姣,冯益平,胡凤丽,陈恩立,任韫卓..鞘氨醇激酶1在肾间质纤维化中的作用及机制研究[J].中国药理学通报,2017,33(2):212-217,218,7.基金项目
河北省卫生厅重点科技研究计划（No 20150628）；河北医科大学大学生创新实验项目资助课题 （）
