摘要/Abstract

摘要： 目的·探讨肾功能快速进展为终末期肾病（end stage renal disease，ESRD）的IgA肾病患者与肾功能长期稳定的IgA肾病患者血清IgA1对体外培养的正常人肾小球系膜细胞（human mesangial cells，HMCs）增殖的刺激作用及对转化生长因子β1（transforming growth factor-β1，TGF-β1）表达水平的影响。方法· 9例经肾活检确诊为原发性IgA肾病的患者，根据病情进展情况分为肾功能快速进展组（n6）和肾功能长期稳定组（n3）。采用亲和层析及分子筛提取血清IgA1；用不同质量浓度（10、50、250、1 000 μg/mL）的IgA1分别干预HMC 12、24 h。CCK8法测定细胞增殖率；real-time PCR测定TGF-β1 mRNA表达；ELISA法测定TGF-β1蛋白表达。结果·肾功能快速进展组及肾功能长期稳定组患者血清IgA1对HMC有明显的促增殖作用，且表现为时间依赖性和浓度依赖性，作用高峰质量浓度分别为250 μg/mL和1 000 μg/mL。2组患者血清IgA1均能显著上调TGF-β1的mRNA和蛋白的表达。在肾功能快速进展组，IgA1质量浓度为10 μg/mL时TGF-β1的mRNA及蛋白水平达到高峰，其后随刺激浓度升高而递减；在肾功能长期稳定组，TGF-β1水平则与血清IgA1呈现平行的浓度依赖性。结论·肾功能快速进展及长期稳定的患者血清IgA1在一定浓度和时间范围内均具有刺激HMC增殖的作用。在较低质量浓度（10～50 μg/mL）范围内，促增殖作用没有明显差异，但肾功能快速进展的患者血清IgA1上调TGF-β1表达的作用更强，提示血清IgA1具有一定的预后评估作用。
关键词: IgA肾病, 肾功能, 系膜细胞, 转化生长因子&, beta, 1
Abstract:
Objective · To extract serum IgA1 patients with IgA nephropathy (IgAN) (end stage renal disease vs long-term srenal function) to explore the effect on proliferation rate of human mesangial cells (HMCs) and the level of transforming growth factor-β1 (TGF-β1). Methods · Nine patients with primary IgAN were divided into rapidly progressive group (n6) and long-term sgroup (n3). Jacalin affinity chromatography and sephacryl S-200HRmolecular sieves were used to distract serum IgA1. HMCs were cultured and co-cultivated with different IgA1 concentration (10, 50, 250 and 1 000 μg/mL)at point of 12 h and 24 h respectively. The proliferation rate was measuredcell counting kit-8 (CCK8). The of TGF-β1 mRNA was measured via quantitative real-time PCR (qRT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect TGF-β1 protein. Results · Serum IgA1 IgAN patients with different renal functions (end stage renal disease vs long-term srenal function) activated proliferation of HMC significantly, presenting with time-dependence and concentration-dependence. The highest value showed at 250 μg/mL and 1 000 μg/mL respectively. Serum IgA1 in two groups of patients statistically increased the of TGF-β1 mRNA and protein. In group with end stage renal disease, the summit stood at 10 μg/mL and started to decreasedegrees afterwards; while in group with long-term srenal function, the level of TGF-β1 increased in a parallel manner with the serum IgA1. Conclusion · Serum IgA1 IgAN patients with different renal functions (end stage renal disease vs long-term srenal function) can both promote the proliferation of HMC. There is no dramatical difference observed with in10-50 μg/mL, but the IgA1 group with end stage renal disease reveals a stronger effect on TGF-β1, in accordance with the pathological type of the patients (IgA sclerosis), suggesting the prognostic value of serum IgA.
Key words: IgA nephropathy, renal function, human mesangial cell, transforming growth factor-&, beta, 1


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