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目的 :观察马兜铃酸Ⅰ致大鼠急性肾损伤的远期效应及其致肿瘤作用。 方法 :采用马兜铃酸Ⅰ[5 0mg/ (kg d) ]连续灌胃 3天 ,建立大鼠急性肾损伤动物模型 ,对大鼠的肾功能及组织形态改变进行长期动态观察。 结果 :马兜铃酸Ⅰ给药后第 8天 ,大鼠肾功能急剧下降 ,表现为大量蛋白尿、糖尿、尿量增加 ,血肌酐、尿素氮、尿NAG酶增高。肾组织病理改变以皮髓交界的急性肾小管坏死为主。给药后 1个月和 3个月大鼠肾功能和组织病理学改变逐渐恢复 ,未见间质炎症和纤维化等慢性病变。给药后 6个月大鼠肾脏肿瘤样增生的发生率为10 0 %;肾脏肿瘤的发生率为 2 8 6 %,包括 3例肾脏间叶性肿瘤和 1例嗜酸细胞腺瘤 ;肾外肿瘤的发生率为 7 1%,为 1例乳腺导管上皮恶性肿瘤。 结论 :马兜铃酸Ⅰ致大鼠急性肾损伤远期效应的特点是大鼠肾功能和肾脏组织病理学改变可逐渐恢复 ,小管间质无明显炎细胞浸润和纤维化等慢性病变 ,但 6个月后出现肾脏和肾外肿瘤。马兜铃酸Ⅰ的致肿瘤作用易被肾功能的恢复所蒙蔽 ,这一点尤其应引起人们的关注。
Objective: To observe the long-term effect of aristolochic acid induced acute kidney injury and its role in tumorigenesis. Methods: Aristolochic acid Ⅰ [50 mg / (kg d)] was given to rats for 3 days continuously to establish animal models of acute kidney injury in rats. The rats were subjected to long-term dynamic observation of renal function and histological changes. RESULTS: On the 8th day after the administration of aristolochic acid Ⅰ, the renal function of rats dropped sharply, showing a large amount of proteinuria. Diabetes and urine volume were increased. Serum creatinine, urea nitrogen and urine NAG were increased. Renal pathological changes to the junction of the acute renal tubular necrosis based. After 1 month and 3 months, the renal function and histopathological changes gradually recovered in rats, and no chronic diseases such as interstitial inflammation and fibrosis were found. The incidence of tumor-like hyperplasia was 10% in rat kidney at 6 months after drug administration; the incidence of renal tumors was 286%, including 3 cases of kidney mesenchymal tumors and 1 case of eosinophilic adenoma; The incidence of tumors was 71%, a case of ductal epithelial malignancy. CONCLUSION: The long-term effect of aristolochic acid induced acute kidney injury in rats is characterized by a gradual recovery of renal function and histopathological changes in rat kidney, no obvious inflammatory cell infiltration and fibrosis in tubulointerstitial lesions, but 6 Kidney and extranodal tumors appeared months later. In particular, the carcinogenic effect of aristolochic acid I should be blinded by the recovery of renal function, which should be of particular concern.