Endoh M, Kashem A, Yamauchi F, Yano N, Nomoto Y, Sakai H, Kurokawa K
Department of Internal Medicine, School of Medicine, Tokai University, Kanagawa, Japan.
Clin Nephrol. 1997 Mar;47(3):168-75.
Thromboxane A2 (TXA2) is a potent vasoconstrictor which is known to be involved in the pathogenesis of experimental glomerulonephritis, although its exact pathogenic significance is not clear in human glomerulonephritis. We have investigated the expression of thromboxane synthase (TXS) in kidney tissues from patients with IgA nephropathy (IgAN), using RT-PCR and immunohistochemical methods. Biopsied renal tissues from thirty-four patients with IgAN (24 whole tissues and 10 isolated glomeruli) and normal renal tissues from 11 nephrectomized kidneys (control, eight whole tissues and three isolated glomeruli) were included in this study. TXS mRNA expression was observed in 10 out of 24 (42%) whole tissue specimens from IgAN, but no such message was disclosed in the control tissue. There was no detectable TXS mRNA expression in the isolated glomeruli either from IgAN patients or controls, although constant mRNA expressions for GAPDH and VPF/VEGF were observed. IgAN patients with positive TXS mRNA had significantly reduced GFR with elevated serum creatinine and serum beta 2-microglobulin levels. Immunostaining, using a monoclonal anti-TXS antibody, identified the localization of the TXS protein in the interstitial areas where monocyte/macrophage infiltration was abundant, as well as in the arterioles of the kidney tissues with advanced tissue damage. It was concluded that TXA2 produced by the interstitial infiltrating cells during the inflammatory process might be involved in the progression of IgA nephropathy.
血栓素A2(TXA2)是一种强效血管收缩剂,已知其参与实验性肾小球肾炎的发病机制,尽管其在人类肾小球肾炎中的确切致病意义尚不清楚。我们使用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法,研究了IgA肾病(IgAN)患者肾组织中血栓素合酶(TXS)的表达。本研究纳入了34例IgAN患者的活检肾组织(24个全组织和10个分离的肾小球)以及11例肾切除肾脏的正常肾组织(对照组,8个全组织和3个分离的肾小球)。在24例IgAN全组织标本中的10例(42%)中观察到TXS mRNA表达,但在对照组织中未发现此类信息。无论是IgAN患者还是对照组的分离肾小球中均未检测到TXS mRNA表达,尽管观察到甘油醛-3-磷酸脱氢酶(GAPDH)和血管通透因子/血管内皮生长因子(VPF/VEGF)的mRNA表达恒定。TXS mRNA阳性的IgAN患者肾小球滤过率(GFR)显著降低,血清肌酐和血清β2-微球蛋白水平升高。使用单克隆抗TXS抗体进行免疫染色,确定TXS蛋白定位于单核细胞/巨噬细胞浸润丰富的间质区域,以及组织损伤严重的肾组织小动脉中。得出的结论是,炎症过程中间质浸润细胞产生的TXA2可能参与IgA肾病的进展。