Yoshida T, Ichikawa Y, Tojo T, Homma M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Lupus. 1996 Apr;5(2):129-38. doi: 10.1177/096120339600500208.
Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1 alpha,2,3-dinor-6-keto-PGF1 alpha and PGE2, and plasma level of 11-dehydro-TXB2, were determined. The effects of four days' dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also studied. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbalance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1 alpha ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2 and urinary TXB2/6-keto-PGF1 alpha ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment. The conclusion reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2 synthetase inhibitor.
本研究探讨了可能影响肾功能的前列腺素代谢异常在狼疮性肾炎中的情况。研究对象包括31例狼疮性肾炎患者、10例非肾性系统性红斑狼疮（SLE）患者以及4例肾性非SLE胶原病患者。测定了尿液中各种前列腺素、血栓素B2（TXB2）、11 - 脱氢 - TXB2、6 - 酮 - PGF1α、2,3 - 二去甲 - 6 - 酮 - PGF1α和前列腺素E2的水平，以及血浆中11 - 脱氢 - TXB2的水平。还研究了选择性血栓素A2（TXA2）合成酶抑制剂DP - 1904（DP）连续给药4天对前列腺素代谢的影响。与非肾性SLE患者相比，狼疮性肾炎患者尿液中反映肾脏TXA2生成的TXB2排泄量显著增加（p < 0.05）。与非肾性SLE患者或健康对照相比，狼疮性肾炎患者尿液中TXB2/6 - 酮 - PGF1α比值也升高（p < 0.01），表明前列腺素失衡，这可能导致肾功能受损及后续病变。这些狼疮性肾炎患者尿液中TXB2/6 - 酮 - PGF1α比值与肌酐清除率呈负相关，与抗DNA抗体滴度呈正相关（p < 0.001）。对8例狼疮性肾炎患者口服DP（400 mg/天，分两次给药），持续4天。所有患者在治疗1至2天后，尿液中TXB2排泄量及尿液TXB2/6 - 酮 - PGF1α比值均下降。8例患者中有4例观察到作为肾功能指标的肌酐清除率升高。此外，在4天治疗期间未引发任何副作用。得出的结论是，狼疮性肾炎中观察到的异常前列腺素代谢可通过血流动力学介导加重肾功能，且这种代谢偏差是可逆的，至少部分可被TXA2合成酶抑制剂纠正。
