阿奇霉素对大鼠阿霉素肾病的干预作用

目的 通过观察阿奇霉素对阿霉素肾病大鼠血、尿生化指标、肾脏组织病理以及细胞间黏附因子1（ICAM-1）、nephrin与podocalyxin在肾组织表达的影响，探讨其在大鼠阿霉素肾病中的干预作用。 方法 建立大鼠阿霉素肾病模型，分为阿奇霉素治疗组、泼尼松治疗组、联合治疗组、模型组及正常对照组。监测实验0、4、8周24 h尿蛋白量（24 h-up）及血生化指标动态变化，计算内生肌酐清除率（Ccr）。观察肾组织病理形态学改变。免疫组化SP法观察肾组织中ICAM-1、nephrin、podocalyxin的表达。 结果 实验4周时尿蛋白及白蛋白指标均达到肾病模型要求，提示模型制作成功。实验8周，与模型组相比，各治疗组大鼠的各项观察指标均有不同程度改善，24 h-up、胆固醇、Scr显著降低（P < 0.05），总蛋白、Alb及Ccr（除外C组）有所增加（P < 0.05），肾组织病理改变减轻，肾脏病理积分及细胞外基质/肾小球面积比值降低（P < 0.01），肾小球及肾小管ICAM-1表达减少（P < 0.01），nephrin、podocalyxin表达增高。综合比较，其中联合治疗组疗效最好。 结论 阿奇霉素对阿霉素肾病大鼠的干预有类似于泼尼松样的治疗作用，但其对早期肾功能的保护作用逊于泼尼松，而二者联合应用可起到协同治疗的作用，其药效明显优于两药的单独应用。

Intervention of azithromycin on adriamycin-induced nephropathy rats

Objective To investigate the effects of azithromycin on serum indicators, urine indicators, renal pathology, intercellular adhesion molecule-1 (ICAM-1), nephrin and podocalyxin in adriamycin(ADR)-induced nephropathy(ADN) rats. Methods ADR nephropathy was induced by a tail intravenous injection of ADR. The rats were randomly divided into azithromycin-treated group, prednisone -treated group, integrated treatment group, model group and control group. Serum index and 24 h urine protein were measured serially at 0, 4th, 8th weeks. The values of creatinine clearance (Ccr) were calculated. Kidney tissues were collected for microscopy observation. The expressions of nephrin, podocalyxin and ICAM-1 in renal tissue were detected by immunohistochemistry SP. Results Compared with normal control group, at the 4th week, 24 hours urine protein and albumin reached the level of ADR nephropathy model. Compared with model group, at the 8th week, 24 h urine protein, cholesterol, serum creatinine, renal pathology changes in the three treated group rats were significantly reduced (P<0.05), serum total protein, albumin and Ccr (except C group) significantly raised (P<0.05), ECM/GA and renal pathology score significantly reduced (P<0.01), ICAM-1 significantly decreased (P<0.01), nephrin and podocalyxin significantly increased. Besides, the curative effect of integrated treatment was better than other treatment group. Conclusions Azithromycin induces similar responses in ADR nephropathy as prednisone, but its early protective effect of renal function is worse than prednisone.The integrated treatment of azithromycin and prednisone has a synergistic effect, and the efficacy is superior to each drug alone.