白藜芦醇通过抑制系膜区细胞增殖下调PDGF-B、TGF-β1表达减缓大鼠IgAN进展

Resveratrol inhibits progression of IgA nephropathyin rats by inhibiting proliferation of mesangial cells anddown regulating expression of PDGF-B and TGF-β1

目的探讨SirT1激动剂白藜芦醇(resveratrol,Res)对IgAN大鼠的治疗效果及其作用机制。方法建立IgA肾病大鼠模型,将大鼠随机分成4组:正常对照组(Control组)、IgA肾病组(IgAN组)、正常对照+Res组(Control+Res组)、IgA肾病+Res组(IgAN+Res组)。丽春红S法检测尿蛋白及自动生化分析仪检测各项生化指标;PAS和Masson染色法观察肾脏病理改变;免疫荧光观测IgA沉积情况;免疫组化法检测PDGF-B、TGF-β1的表达。结果与IgAN组相比,白藜芦醇干预组24 h尿蛋白量、尿素氮、血肌酐表达明显降低,肾小球IgA荧光沉积明显减少;IgAN组后期系膜区细胞及基质增生、肾小球体积增大均受到明显抑制;白藜芦醇还显著降低IgAN组PDGF-B、TGF-β1的高表达。结论白藜芦醇能够显著减少IgA肾病大鼠肾脏IgA免疫复合物在系膜区的沉积,并通过抑制系膜区细胞增殖下调PDGF-B及TGF-β1的表达来减轻肾小球硬化,从而起到减缓大鼠IgA肾病进展的作用。

Aim To investigate the therapeutic effect of SirT1 agonist resveratrol on IgA nephropathy rats and its mechanisms.Methods An IgA nephropathy rat model was established.The rats were divided into four groups randomly:control group,IgA nephropathy group,control treated with Res group and IgA nephropathy treated with Res group.The urine protein was detected by Ponceau S;the biochemical indexes were detected by automatic biochemical analyzer;the pathological changes of kidney were observed by PAS and Masson staining;IgA deposition was observed by immunofluorescence;the expressions of PDGF-B and TGF-β1 were detected by immunohistochemistry.Results Compared with IgA nephropathy group,the volume of 24-hour urinary protein and the expression of BUN and Scr in Res group decreased significantly,and the fluorescence of IgA in glomerulus was less in resveratrol group;mesangial cells and matrix proliferated and glomerular volume increased in IgA nephropathy group at the later stage,and both of them were significantly inhibited.Resveratrol could significantly reduce the high expression of PDGF-B and TGF-β1 in IgA nephropathy group.Conclusions Res can inhibit the deposition of IgA immune complex in mesangial region of IgA nephropathy rats and reduce glomerulosclerosis by down-regulating the expression of PDGF-B and TGF-β1,in turn it suppresses cell proliferation in mesangial region.It suggests that resveratrol plays an important role in slowing down the progression of IgA nephropathy.