Tanda K, Seki T, Kobayashi S, Kanagawa K, Chikaraishi T, Togashi M, Nonomura K, Koyanagi T
Department of Urology, Hokkaido University School of Medicine, Sapporo, Japan.
Int J Urol. 1994 Dec;1(4):309-15. doi: 10.1111/j.1442-2042.1994.tb00055.x.
To investigate the possible involvement of endogenous endothelin (ET) in cyclosporin A (CsA) nephrotoxicity, we examined the renal effects of the selective [125I]ET-1 binding to porcine aortic membrane (ETA) receptor antagonist, BQ-123 (BQ), on CsA-treated rats. An osmotic minipump filled with BQ or its vehicle (saline), was subcutaneously implanted and animals were treated with CsA (50 mg/kg/d, i.p.) for 4 d. In both BQ- and its vehicle-treated rats, the 24-hour urine volume, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, urinary Ca/creatinine (Cr) and urinary NAG/Cr ratios were significantly increased compared with those before administration of CsA. In contrast, after administration of CsA, urinary Cr excretion was significantly decreased in both rat groups. Although urinary NAG excretion and the NAG/Cr ratio in the rats treated with BQ were significantly increased compared with those treated with saline, the serum Cr levels in BQ-treated rats were significantly lower than those in saline-treated rats. Urinary immunoreactive ET-1 (irET-1) excretion in all animals was significantly increased after administration of CsA. There were no significant differences in urinary irET-1 excretion in both BQ-treated and saline-treated rats with and without CsA. Expression of irET-1 was seen in the cytoplasm of renal tubules, but the degree of expression was similar in the BQ-treated and saline-treated rats on CsA. In the BQ-treated rats, small round areas with high grain densities over the glomeruli in the cortex and vesa recta bundles in the outer medulla were masked by the antagonist action of BQ.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究内源性内皮素（ET）是否可能参与环孢素A（CsA）的肾毒性作用，我们检测了选择性[125I]ET-1与猪主动脉膜（ETA）受体拮抗剂BQ-123（BQ）对CsA处理大鼠的肾脏影响。将充满BQ或其赋形剂（生理盐水）的渗透微型泵皮下植入，动物腹腔注射CsA（50mg/kg/d），持续4天。与给予CsA前相比，BQ处理组和赋形剂处理组大鼠的24小时尿量、尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）排泄量、尿钙/肌酐（Cr）和尿NAG/Cr比值均显著增加。相反，给予CsA后，两组大鼠的尿Cr排泄量均显著降低。虽然与生理盐水处理组相比，BQ处理组大鼠的尿NAG排泄量和NAG/Cr比值显著增加，但BQ处理组大鼠的血清Cr水平显著低于生理盐水处理组。所有动物给予CsA后，尿免疫反应性ET-1（irET-1）排泄量均显著增加。给予或未给予CsA的BQ处理组和生理盐水处理组大鼠的尿irET-1排泄量均无显著差异。irET-1表达见于肾小管细胞质，但给予CsA的BQ处理组和生理盐水处理组大鼠的表达程度相似。在BQ处理组大鼠中，皮质肾小球和外髓直小血管束上高颗粒密度的小圆形区域被BQ的拮抗作用掩盖。（摘要截短于250字）
