中国病理生理杂志Issue(4)：719-724,6.DOI:10.3969/j.issn.1000-4718.2015.04.026
帕立骨化醇抑制糖尿病肾病大鼠肾小管间质纤维化
Influence of paricalcitol on renal tubulointerstitial fibrosis in diabetic ne-phropathy
摘要
Abstract
[ ABSTRACT] AIM:To investigate the effect of paricalcitol ( P) on renal tubulointerstitial fibrosis and the under-lying mechanisms in diabetic nephropathy ( DN) .METHODS:DN rat model was induced by a single intraperitoneal in-jection of streptozotocin after fasting.The animals were randomly divided into 2 groups: the DN rats in paricalcitol-inter-vened group ( group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4μg/kg (3 times a week);the DN rats in DN group ( group D) were given isopyknic propylene glycol.Normal control group ( group C) was also set up.The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks.The biochemical indexes were measured.The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4,β-catenin and Klotho by immunohistochemistry and Western blotting.In addition, the correlation among the above indexes was analyzed.RESULTS:(1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D ( P<0.05 ) .( 2 ) The area of renal tubulointerstitial fibrosis in-creased in group D compared with group C, while decreased in group P compared with group D (P<0.05).(3) The ex-pression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05).Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 andβ-catenin decreased in group P (P<0.05).(4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 andβ-catenin (P<0.05).CONCLUSION:Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.关键词
帕立骨化醇/糖尿病肾病/肾小管间质纤维化/Wnt/β-catenin信号通路/Klotho蛋白Key words
Paricalcitol/Diabetic nephropathy/Renal tubulointerstitial fibrosis/Wnt/β-catenin signaling pathway/Klotho protein分类
医药卫生引用本文复制引用
王来亮,罗群,蔡珂丹,周芳芳,高燕红..帕立骨化醇抑制糖尿病肾病大鼠肾小管间质纤维化[J].中国病理生理杂志,2015,(4):719-724,6.基金项目
浙江省医药卫生科研基金资助项目（No．2012KYB175）；宁波市自然科学基金资助项目 （）
