化学诱导大鼠多发肾囊肿伴肾肿瘤及肾组织DNA损伤的表达

Chemical induced polycyst with renal tumor and expression of 8 OHdG in kidney tissue

目的 观察化学药物大鼠多发肾囊肿伴肾肿瘤模型的诱发情况和DNA损伤标记物 8 羟基脱氧鸟苷 (8 OHdG)在其肾组织的表达。 方法 用 2 氨基 4,5 二苯噻唑 (DPT)和N 亚硝基吗啉 (NNM)诱发与人类获得性肾囊肿 (ACDK)伴肾癌相似的大鼠动物模型。并用免疫组化方法 (LSAB法 )检测 8 OHdG在大鼠肾组织的表达。 结果 在本实验中 ,NNM组 3/ 10的大鼠诱发肾肿瘤出现。在DPT/NNM组的 9只大鼠均发生双侧肾脏多发囊性变化 ,7/ 9大鼠有肾肿瘤的发生 ,其中 4例肾肿瘤发生于囊肿上皮细胞并向囊腔内生长。用DPT/NNM诱发大鼠模型的病理改变与人类ACDK极为相似。在上述两实验组的大鼠肾脏组织中发现肾小管上皮、囊肿上皮、间质细胞及肿瘤细胞均有 8 O HdG的明显表达。 结论 用DPT和NNM能诱发与人类获得性肾囊肿 (ACDK)伴肾癌相似的大鼠动物模型 ,并能造成相似的病理改变和DNA损伤标记物 8 OHdG的明显表达 ,两者可能存在某些相似的发病机制。

HUANG Xiaobo, WANG Xiaofeng, ZHU Jichuan, et al. Department of Urology, People′s Hospital, Beijing Medical University, Beijing 100044,China. Absrtact Objective To induce the rat model of polycyst with renal tumor and investigate the expression of 8 OHdG in the kidney tissues. Methods The rat model of polycyst with renal tumor, similar to human acquired cystic disease of the kidney (ACDK), was induced by oral administration of 2 amino 4,5 diphenylthiazole (DPT) and N nitrosomorpholine (NNM). Immunohistochemical method (LSAB) was used to assay the expression of 8 hydroxydeoxyguanosine (8 OHdG) in the rat kidney tissue. Results Three of 10 rats in the NNM group had renal solid adenomatous lesions. Bilateral polycysts were observed in all 9 rats of the DPT/NNM group. Seven of the 9 rats had cystic multistage renal tumor. In the DPT/NNM group, 4 rats had cystic adenomatous lesions, but none in the other groups showed this lesion. In the model, adenomatous lesions derived from polycysts in the rats were closely consistent to human ACDK in morphology. The significant expression of 8 OHdG was found on renal tubular cell, cystic epithelial cell, stromal cell and tumor cell in all rats of the NNM and DPT/NNM group. Conclusion A rat model of polycysts with renal tumor, similar to human ACDK, induced by DPT and NNM provides evidences for further study on pathogenic mechanism in human ACDK with renal cell carcinoma. The expression of 8 OHdG, a DNA damage marker, in the renal tissues of rat model might help to explain the mechanism of cysticogenesis and carcinogenesis in human ACDK.