大鼠慢性移植肾肾病动物模型的制作经验总结

Establishment of rat experiment model of chronic allograft nephropathy

目的总结制作稳定的大鼠慢性移植肾肾病（CAN）动物模型的经验。方法以F344近交系大鼠为供者，取供者左肾作为供肾，原位低温灌注；以Lewis近交系大鼠为受者，行左侧原位肾移植，供肾动脉与受者腹主动脉端侧吻合，供肾静脉与受者肾静脉端端吻合，输尿管带膀胱瓣与受者膀胱吻合。术后用环孢素A灌胃10d，剂量为10mg·kg^-1·d^-1。每月采集受者血液和尿液，测定血肌酐及24h尿蛋白，分别于术后2、4个月获取移植肾进行病理检查。结果45只进行移植，手术成功率为85％，单次手术时间为（120±20）min。移植后1个月，大鼠即出现血肌酐、尿素氮及血胱抑素升高，24h尿蛋白增加，与术前相比，各项指标均升高（P〈O．05）；术后2个月及4个月，除尿蛋白继续增加外，其余观察指标上升不明显。移植术后2个月，移植肾有轻度至中度的间质纤维化，淋巴细胞和浆细胞的浸润；4个月时，移植肾可见广泛的间质纤维增生，间质细胞大量浸润，肾小球基底膜增厚、硬化、闭塞，肾小管萎缩退化，符合CAN的病理改变。结论通过充分的手术强化训练及改进，规范大鼠取。肾、移植术中、术后管理的每个细节，大鼠CAN模型的成功率及稳定性高。

Objective To summarize the experience of establishing the stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After the left kidney of the donor perfused in situ under hypothermic condition, the left renal vein, abdominal aorta and bladder flap of the donor was anastomosed with the left renal vein, renal artery and bladder of the recipient, respectively. The recipients were given cyclosporin oral solution 10 mg/kg every day by gavage for 10 days after transplantation. The blood and urine samples were collected 1 month, 2 months and 4 months after transplantation and renal function and total urine protein were examined. The pathological changes of the renal allograft were observed 2 and 4 months after transplantation. Results Forty-five rats received operation and achievement ratio was 85%. The renal transplantations were finished in 120 ± 20 rain. The Scr, BUN, Cycs and total urine protein demonstrated a significant increase one month after transplantation. On the second and fourth month, with the exception of urine protein continued to increase, the other indicators did not change significantly. Two months after transplantation renal pathology demonstrated light to moderate interstitial fibrosis, infiltration of lymphocytes and plasma cells. At 4th month the renal allografts showed extensive interstitial fibrosis, a large number of infiltrating interstitial cells, thickening, hardening, occlusion of glomerular basement membrane, and renal tubular atrophy that were consistent with pathological changes of chronic allograft nephropathy. Conclusion Through adequate surgical training and improvement, and specification for rat nephrectomy, transplantation surgery, and postoperative management in every detail, the model with high success rate and stability can be achieved.