三聚氰胺氰尿酸盐致SD大鼠肾脏毒性的研究  

Experimental Study Nephrotoxicity of Melamine Cyanurate

作　　者：于永刚[1] 廖松柏[1] 于管天[2] 武英杰[1] 刘为池[1] 刘刚[1] 廖桂祥[1] 

机构地区：[1]解放军第181医院泌尿外科,广西桂林541002 [2]南方医科大学

出　　处：《临床泌尿外科杂志》2011年第6期465-470,共6页Journal of Clinical Urology

摘　　要：目的:研究三聚氰胺氰尿酸盐的肾脏毒性。方法:90只SPF级SD大鼠,雌雄各半,体重(200±10)g,随机分为2个给药组和空白对照组,每组各30只。给药组分别给予三聚氰胺氰尿酸盐60 mg/(kg·d^(-1))、200mg/(kg·d^(-1))。各组大鼠每天1次连续灌胃,空白对照组灌胃无菌水2 ml/(只·d^(-1))。用代谢笼收集前7天24h尿液,进行24 h尿量和24 h尿酸排泄量测量及尿沉渣涂片检查;分别于第4、14、31、45、60天灌胃前每组处死6只大鼠做血液生化检测、脏器系数计算,取肾脏用外科显微镜观察后常规制片,观察肾脏病理及晶体形成。结果:与对照组比较实验组大鼠尿量增多(P<0.05),60 mg/(kg·d^(-1))组尿量增多更加明显,与200 mg/(kg·d^(-1))组大鼠尿量比较差异也有统计学意义(P<0.05)。给药组大鼠血清胱抑素随着剂量的增高及时间的延长逐渐升高但是血尿酸浓度却随着剂量的增高及时间的延长而逐渐降低(P<0.05)。实验组均在第31后天测得血肌酐、血尿素氮、血清胱抑素C升高(P<0.01)。给药组尿沉渣涂片发现特异性晶体。实验组给药31天解剖开始发现大鼠肾脏开始出现肿大呈灰黄色、结构不清,许多淡黄色颗粒沉积于皮髓交界处,形成黄色弧形带。部分肾脏有点状或片状出血灶,病理切片发现许多淡黄色、半透明同心圆形晶体,主要集中在肾小管,但是60 mg/kg组病理改变明显较200 mg/kg组轻。之前时间点灌药组肾脏大体标本及病理切片均未见晶体形成,病理切片仅见少量肾小管轻度扩张及小管上皮肿胀。结论:使用一定剂量三聚氰胺氰尿酸盐连续灌胃也会导致大鼠的肾脏内会形成三聚氰胺氰尿酸盐晶体,并在晶体形成前已经造成肾小球滤过功能受损,此晶体能堵塞肾小管造成肾脏损害甚至急性肾衰竭;同时三聚氰胺氰尿酸盐具有一定的利尿作用,并能影响尿酸的代谢降低血尿酸的浓度。Objective： To explore the oral nephrotoxicity of melamine cyanurate in the kidneys of SD rats. Method：In this randomized, pilot study 90 SPF SD rats were randomly assigned into 3 groups （30 each group） according to their different doses of melamine cyanurate Ctrl,60, 200 mg/（kg· d-1 ）%, which were given daily by stomach perfusion for 60 consecutive days,respectively. Six rats in each group were confined in metabolism cages for the first week,and urine samples were collected over a 24 h period. Blood samples and kidney sections were evaluated on days 4,14,31,45 and 60. Result： Urine volume of rats in experimental groups were significantly higher than that of normal controls （P〈0.05） ,and there was also notale difference in urine volume between experimental group. After oral administration of melamine cyanurate, the level of serum cystatin C was increased significantly, while serum uric acid decreased markedly as compared with the control group （P〈0.05）. Specific crystals were found in the urinary sediment smears. There were significantly higher levels of BUN, serum cystatin C and creatinine in the blood of rats in the experimental groups （30-60 days）, than those of control group （P〈0.01）. In the200 mg/kg/ day-treated group （30-60 days） and,an typical appearance of large, yellow and edematous kidney was seen by grossly. Pathological sections showed that a number of yellow, semi-transparent and concentric round crystals were deposited in renal tubules. The pathologic changes in 200 mg/kg group were severer than that in 60 mg/kg group. Conclusion：The results demonstrate that administration by garage melamine cyanurate induce crystal formation and affected renal functioning as well as oral administration the mixture of melamine and cyanurlc acid. Melamine cyanurate reduce the concentration of serum uric acid.

关 键 词：三聚氰胺氰尿酸盐 肾功能衰竭 肾结石 

分 类 号：R692.4[医药卫生—泌尿科学]