Nakazawa Tomomi, Kasahara Kenichiro, Ikezaki Shinichiro, Yamaguchi Yuko, Edamoto Hiroshi, Nishimura Nobuo, Yahata Megumi, Tamura Kazutoshi, Kamata Eiichi, Ema Makoto, Hasegawa Ryuichi
J Toxicol Pathol. 2009 Jun;22(2):125-31. doi: 10.1293/tox.22.125. Epub 2009 Jul 7.
In this study, we investigated the sequential changes in the development of renal tubular cysts in newborn rats treated with p-cumylphenol (PCP). Fifteen animals per sex were treated orally with 300 mg/kg/day of PCP for up to 18 days from postnatal day (PND) 4 and were sacrificed on PNDs 8, 12, 19 and 22 and after a 7 day recovery period. On PNDs 8 and 12, slight dilatation of the collecting ducts was frequently observed in the medulla and slight papillary necrosis was also noted in some cases. These dilated collecting ducts were lined with slightly hyperplastic epithelial cells. On PNDs 19 and 22, multiple large cystic changes arising from the collecting ducts in the outer medulla were seen. These cystically dilated ducts were also lined with hyperplastic epithelial cells. During the dosing period, the labeling index of proliferating cell nuclear antigen in the collecting duct epithelium was higher in the PCP-treated group than in the control group at all time points. After a 7 day recovery period, the cystic change still remained, although the cell density was decreased and the epithelial cells became flattened. On the other hand, basophilic tubules with peritubular lymphoid cell infiltration were multifocally observed in the cortex. In conclusion, PCP induced multiple renal cysts that developed in the collecting ducts of the outer medulla in neonatal rats, and it is suggested that epithelial cell proliferation may play some roles in the induction of cystic lesions.
在本研究中,我们调查了对叔辛基苯酚(PCP)处理的新生大鼠肾小管囊肿发育过程中的序贯变化。从出生后第4天(PND)开始,每组15只雌雄动物口服300mg/kg/天的PCP,持续18天,并在PND 8、12、19和22以及7天恢复期后处死。在PND 8和12时,经常在髓质中观察到集合管轻度扩张,在某些情况下还发现轻度乳头坏死。这些扩张的集合管内衬有轻度增生的上皮细胞。在PND 19和22时,在外髓质集合管处可见多个大的囊性改变。这些囊性扩张的导管也内衬有增生的上皮细胞。在给药期间,PCP处理组集合管上皮中增殖细胞核抗原的标记指数在所有时间点均高于对照组。7天恢复期后,尽管细胞密度降低且上皮细胞变扁平,但囊性改变仍然存在。另一方面,在皮质中多灶性观察到伴有肾小管周围淋巴细胞浸润的嗜碱性小管。总之,PCP诱导新生大鼠外髓质集合管出现多个肾囊肿,提示上皮细胞增殖可能在囊性病变的诱导中起一定作用。