Seppälä E, Lehtinen K, Isomäki H, Nissilä M, Harmoinen A, Mörsky P, Koivula T, Vapaatalo H
Department of Biomedical Sciences, University of Tampere, Finland.
Int J Clin Pharmacol Res. 1988;8(3):149-56.
The effects of long-term aurothiomalate and D-penicillamine treatments on renal function and the urinary excretion of prostanoids were studied in 20 patients with classic or definite rheumatoid arthritis. Twelve-hour urine was collected overnight, on the following day blood samples were taken in the morning and 12-hour urine was collected during the following day. Albumin excretion into the urine was determined by a sensitive quantitative method. Beta-2-microglobulin (B2MIGLO) and N-acetyl-beta-glucosaminidase (NAG) serum concentrations and excretions into the urine were measured to detect possible tubular or glomerular damage, respectively. The excretions of prostaglandin E2 (PGE2), thromboxane B2 and 6-keto-PGF1 alpha into urine were determined. In the aurothiomalate group, albumin excretion ranged 1-16 mg/12 h, and in the penicillamine group 0.8-31 mg/12 h. In the penicillamine group, but not in the aurothiomalate group, total protein, B2MIGLO and PGE2 excretions were higher (p less than 0.05) during the daytime than during the night. The daytime excretion of PGE2 was higher (p less than 0.01) in the penicillamine than in the aurothiomalate group. In the penicillamine group B2MIGLO excretion into urine correlated (p less than 0.01) with PGE2 excretion in the daytime. According to the results, not even long-term aurothiomalate treatment affects renal prostanoid excretion, while penicillamine increases urinary PGE2 excretion. This could be related either to the cofactor-like activity of penicillamine in the prostanoid synthesis or to damage in tubular cells. The role of prostanoids in maintaining blood flow and filtration may be more important in patients with renal damage than in normal conditions.
对20例典型或确诊的类风湿关节炎患者研究了长期金硫代苹果酸盐和青霉胺治疗对肾功能及前列腺素尿排泄的影响。过夜收集12小时尿液,次日早晨采集血样,并在次日收集12小时尿液。采用灵敏的定量方法测定尿白蛋白排泄量。分别测定血清β2微球蛋白(B2MIGLO)和N - 乙酰 - β - 氨基葡萄糖苷酶(NAG)浓度及尿排泄量,以检测可能的肾小管或肾小球损伤。测定尿中前列腺素E2(PGE2)、血栓素B2和6 - 酮 - PGF1α的排泄量。金硫代苹果酸盐组尿白蛋白排泄量为1 - 16mg/12小时,青霉胺组为0.8 - 31mg/12小时。在青霉胺组而非金硫代苹果酸盐组,白天总蛋白、B2MIGLO和PGE2排泄量高于夜间(p < 0.05)。青霉胺组白天PGE2排泄量高于金硫代苹果酸盐组(p < 0.01)。在青霉胺组,白天尿B2MIGLO排泄量与PGE2排泄量相关(p < 0.01)。根据结果,即使长期金硫代苹果酸盐治疗也不影响肾前列腺素排泄,而青霉胺可增加尿PGE2排泄。这可能与青霉胺在前列腺素合成中的辅因子样活性或肾小管细胞损伤有关。前列腺素在维持血流和滤过中的作用在肾损伤患者中可能比在正常情况下更重要。