三聚氰胺诱导大鼠肾脏损伤和尿路结石形成的研究

Development and formation of urinary calculi and renal injury in rats administered with melamine

目的:观察三聚氰胺(Mel)诱导大鼠肾脏损伤和尿路结石形成的病理演变过程并探讨其诱导机制。方法:采用含3%(W/W)Mel的饲料诱导喂养雄性SD大鼠1-4个月。先分2组:A为空白组(n=14);B为Mel组(n=40)。3个月后将B组随机分3组:B1停喂Mel饲料;B2停喂Mel饲料,并饮含1%(W/V)友莱特的水;B3继续喂含3%(W/W)Mel饲料。定期收集大鼠24h尿液检测pH、肌酐、尿酸、蛋白和Mel水平,观察大鼠死亡情况并对死亡和即将死亡的大鼠进行组织病理分析。第3个月A、B组各随机处死8只大鼠,采血检测肌酐,观察尿路肿瘤和结石形成情况并分析结石成分,进行肾脏病理分析。至第4个月实验结束处死全部大鼠,进行以上相关指标检测。结果:与A组比较,B组大鼠尿液Mel的水平随药物暴露时间增加而增加,同时肾脏损伤加重,但各组尿pH无明显差异。诱导后6周即观察到膀胱内大量结石形成,结石成分为三聚氰胺磷酸盐,无尿酸;未观察到输尿管结石形成。病理分析见髓质区肾小管腔内Mel晶体沉积,肾脏上皮和间质损伤明显,并随着药物暴露时间的增加肾脏炎症和纤维化进行性发展。但诱导4个月未发现膀胱肿瘤。诱导3个月后停药2周,尿液中已经检测不到Mel。停药后4周,全部大鼠膀胱均未发现结石存在,而大鼠肾功能明显改善,肾脏病理损伤情况减轻。另外,与B1组比较,使用友莱特(B2组)可促进大鼠肾功能的改善。结论:Mel可诱导大鼠肾脏损伤和尿路结石形成,两者的发生与药物的暴露时间和尿液Mel浓度有关;尿路结石不是肾脏损伤发生的主要因素,停止药物接触肾功能可部分恢复,同时尿路结石可自行消失;而使用友莱特治疗可改善大鼠的肾功能。

AIM： To investigate the formation of urinary calculi and the development of renal injury in rats administered with melamine.METHODS： The renal lesions and the formation of urinary calculi induced by administration of melamine were investigated in male SD rats. The animals, 6 weeks old at the beginning of the experiment, were treated with 3%（W/W） melamine in the diet for 12 weeks followed by a 4-week period without the chemical. The treatment with Uralyt-U was also performed.RESULTS： The total observation time was 16 weeks. The renal lesions （100%） and urinary calculus formation （54.5%） were observed in the rats given 3% melamine. However, carcinomas of the urinary bladder were not found. Withdrawal of melamine resulted in the improvement of renal lesions and the vanishing of the urinary calculus. Treatment with Uralyt-U improved the renal function. CONCLUSION： It is confirmed that melamine at the dose of 3% in the diet induces the formation of urinary calculi and development of renal injury in rats. Urinary calculi are not the direct cause of renal injury. Withdrawal of melamine results in improvement of renal lesions and vanishing of the urinary calculi.