IgA肾病早期肾脏局部RAS的活化与调节

目的观察IgA肾病早期肾脏局部肾素血管紧张素系统(renin-angiotensin system,RAS)的活化状态和调节,及其与转化生长因子-β1(transforming growth factor,TGF-β1)的关系,为临床选择适宜用药时机提供实验依据。方法选取肾穿确诊的原发性IgA肾病、且无影响RAS因素的患儿共38例。按肾小球系膜增生程度分组,选择远离瘤体的正常肾组织为正常对照组。采用免疫组化法检测血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 recep-tor,AT1R)、TGF-β1,原位杂交法检测AT1RmRNA,均为石蜡切片。用计算机图像处理系统进行免疫组化和原位杂交结果分析。结果正常对照组AngⅡ、AT1R、AT1RmRNA和TGF-β1表达微弱。IgA肾病患者各因子表达明显增多,早期组的表达水平即明显高于正常对照组。各因子间存在复杂的相关性。结论IgA肾病早期AngⅡ已经活化,推测在IgA肾病早期应用RAS阻滞剂可能有利于遏制疾病的发展。

The Renal Local Activation and Regulation of RAS in the Early Stage of IgA Nephropathy

Objective This study was carried out to investigate the role of the RAS in the early stage of IgA nephropathy with the aim of providing experimental basis for clinical selection of appropriate drugs.Methods There were 38 biopsy-proven primary IgA nephropathy(IgAN) patients.According to the degree of mesangial proliferation,we divided them into two groups: the groupⅠ of mild mesangial proliferation was to be designated as early IgAN group,the groupⅡ of moderate and severe mesangial proliferation was to be designated as progressive IgAN group.Subjects for normal control group were taken from normal portions of renal cell carcinoma at the time of surgery.Immunohistochemistry methods were used to study the expression of angiotensin Ⅱ(AngⅡ),angiotensin type 1 receptor(AT₁R),transforming growth factor-β1(TGF-β1),and the detection of AT₁R mRNA by in situ-hybridization on the paraffin-embbedded sections.The percentage of the labeled surface area was evaluated by using a computer Imaging System.Results In normal kidney,AngⅡ AT₁RmAT₁RmRNA and TGF-β1 are all expressed tracely,in samples from early IgAN patients,a marked increase of the expressions was observed.On the glomerules,AngⅡ expression was significantly higher in progressive group than early IgAN group(P=0.032).There were complex correlations among the factors.Conclusion The renal local AngⅡ had been activated in the early stage of IgA nephropathy. The earlier use of RAS inhibitors may inhibit the progress of IgA nephropathy.