Suzuki S, Kuroda T, Kazama J I, Imai N, Kimura H, Arakawa M, Gejyo F
Department of Clinical and Laboratory Medicine, Fukui Medical University, Matsuoka, Japan.
J Am Soc Nephrol. 1999 Feb;10(2):264-70. doi: 10.1681/ASN.V102264.
To evaluate the role of leukotriene B4 (LTB4) in glomerulonephritis, this study was conducted to examine whether ONO-4057, an LTB4 receptor antagonist, moderated nephritis caused by the injection of nephrotoxic serum (NTS) into Wistar-Kyoto rats. Rats were given intraperitoneal injections of ONO-4057 or phosphate-buffered saline 24 h before the injection of NTS. These rats subsequently received equal doses of ONO-4057 or phosphate-buffered saline 3 h and 1, 2, 3, 4, 5, and 6 d later. Compared with the control groups, ONO-4057 treatment significantly reduced proteinuria and hematuria, suppressed the glomerular accumulation of monocytes/macrophages, and reduced the formation of crescentic glomeruli in a dose-dependent manner. These results suggest that LTB4 is responsible for the crescentic formations and renal dysfunction associated with NTS nephritis. The LTB4 receptor antagonist ONO-4057 may thus be beneficial in the treatment of crescentic glomerulonephritis.
为了评估白三烯B4（LTB4）在肾小球肾炎中的作用，本研究旨在检测LTB4受体拮抗剂ONO-4057是否能减轻向Wistar-Kyoto大鼠注射肾毒性血清（NTS）所引起的肾炎。在注射NTS前24小时，给大鼠腹腔注射ONO-4057或磷酸盐缓冲盐水。随后，这些大鼠在3小时以及1、2、3、4、5和6天后接受等量的ONO-4057或磷酸盐缓冲盐水。与对照组相比，ONO-4057治疗显著降低了蛋白尿和血尿，抑制了单核细胞/巨噬细胞在肾小球的积聚，并以剂量依赖的方式减少了新月体性肾小球的形成。这些结果表明，LTB4与NTS肾炎相关的新月体形成和肾功能障碍有关。因此，LTB4受体拮抗剂ONO-4057可能对新月体性肾小球肾炎的治疗有益。
