Yamamoto Emi, Izawa Takeshi, Juniantito Vetnizah, Kuwamura Mitsuru, Yamate Jyoji
Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
J Toxicol Pathol. 2010 Dec;23(4):271-5. doi: 10.1293/tox.23.271. Epub 2010 Dec 16.
Cisplatin, an anticancer drug, is well known to have nephrotoxicity as an adverse effect. We investigated the expressions of cell cycle markers and prostaglandin E(2) (PGE(2)) receptors (EP) in the affected renal tubules in rats injected with a single dose (6 mg/kg body weight) of cisplatin. On days 1-3 after dosing, the affected renal epithelial cells were almost desquamated, showing necrosis. On day 5 onwards, the renal tubules were rimmed by flattened or cuboidal epithelial cells with basophilic cytoplasm; BrdU-immunopositive cells began to significantly increase, indicating regeneration. Simultaneously, TUNEL-positive apoptotic cells were also seen. On days 1-5, cyclin D1-immunopositive cells were decreased with an increased expression in p21 mRNA, indicating G(1) arrest in the cell cycle. The affected renal epithelial cells began to react to EP4 receptor, but not to EP2 receptor. Some EP4 receptor-reacting epithelial cells gave a positive reaction to BrdU or cyclin D1. Collectively, the affected renal tubules underwent various alterations such as necrosis, apoptosis, regeneration and G(1) arrest; the aspects might be influenced by endogenous PGE(2) through EP4 receptor.
顺铂是一种抗癌药物，众所周知其具有肾毒性这一副作用。我们研究了单次注射剂量为6毫克/千克体重的顺铂的大鼠中，受影响肾小管中细胞周期标志物和前列腺素E2（PGE2）受体（EP）的表达情况。给药后第1至3天，受影响的肾上皮细胞几乎完全脱落，呈现坏死状态。从第5天起，肾小管被扁平或立方形上皮细胞围绕，这些细胞具有嗜碱性细胞质；BrdU免疫阳性细胞开始显著增加，表明正在再生。同时，也可见TUNEL阳性凋亡细胞。在第1至5天，细胞周期蛋白D1免疫阳性细胞减少，p21 mRNA表达增加，表明细胞周期中G1期停滞。受影响的肾上皮细胞开始对EP4受体产生反应，但对EP2受体无反应。一些对EP4受体产生反应的上皮细胞对BrdU或细胞周期蛋白D1呈阳性反应。总体而言，受影响的肾小管经历了坏死、凋亡、再生和G1期停滞等各种变化；这些情况可能受到内源性PGE2通过EP4受体的影响。
