Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations.
Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations.
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发表时间：
1980-06
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通讯作者：
D. Dobyan;J. Levi;C. Jacobs;J. Kosek;M. Weiner
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作者：
D. Dobyan;J. Levi;C. Jacobs;J. Kosek;M. Weiner
在腹腔注射顺式二胺二氯铂后1、2、3、5、7天，采用光镜、透射电镜和扫描电镜观察肾脏形态学变化并定位损伤部位。注射该药3天后病理改变明显，并局限于位于外髓质外条纹的近端小管S3段。在S3节段可见一系列变化，包括刷状边缘变薄或局灶性丧失，细胞肿胀，核染色质凝结和局灶性坏死。5天后，主要表现为外条S3节广泛的管状坏死。坏死的小管上皮细胞从基底层脱离，脱落到小管腔内。在许多地区只剩下光秃秃的基板。7天后，S3节段再生，其特征是小管具有广泛扩张的管腔，管腔内排列着许多低位上皮细胞。顺式二胺二氯铂对位于外髓质外条纹的近端小管S3段的肾毒性作用的观察表明，这种抗肿瘤药物产生的损伤模式与其他急性肾衰肾毒性和缺血性模型相似。
Light microscopy, transmission electron microscopy and scanning electron microscopy were used to characterize the morphologic alterations and to localize the site of injury within the kidney 1, 2, 3, 5 and 7 days after the intraperitoneal injection of cis-diamminedichloroplatinum. Pathologic alterations were evident 3 days after the injection of the drug and were localized to the S3 segment of the proximal tubule situated in the outer stripe of the outer medulla. A spectrum of changes was seen in this S3 segment which included a thinning or focal loss of brush border, cellular swelling, condensation of the nuclear chromatin and focal areas of necrosis. After 5 days, widespread tubular necrosis of the S3 segment in the outer stripe was the predominant finding. Necrotic tubular epithelial cells could be seen detaching from the basal lamina and being sloughed into the tubular lumen. Only a bare basal lamina remained in many areas. Regeneration of the S3 segment was seen after 7 days and was characterized by tubules with widely dilated lumens which were lined by many low-lying epithelial cells. The observation that cis-diamminedichloroplatinum exerts its nephrotoxic effect on the S3 segment of the proximal tubule located in the outer stripe of the outer medulla demonstrates that the pattern of injury produced by this antitumor drug is similar to that associated with other nephrotoxic and ischemic models of acute renal failure.