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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 investigate the renal toxicity of melamine cyanurate. Methods: Ninety Sprague-Dawley (SD) SD rats, male and female, weighing 200 ± 10 g, were randomly divided into two treatment groups (n = 30) and a control group (n = 30). The administration group were given melamine cyanurate 60 mg / (kg · d -1), 200 mg / (kg · d -1) respectively. The rats in each group were given continuous gavage once a day, while the blank control group was given 2 ml / (d · (-1)) sterile water. Urine was collected 7 days before and 24 h with metabolic cage, 24 h urinary excretion and 24 h urinary excretion were measured and urinary sediment smear was examined. Each group was sacrificed on the 4th, 14th, 31st, 45th and 60th day after gavage Only rats do blood biochemical tests, organ coefficient calculation, the kidneys were observed with a surgical microscope conventional production, to observe the pathological changes of kidney and crystal formation. Results: Compared with the control group, the excretion of urine in the experimental group increased (P <0.05), and the excretion of urine in the group of 60 mg / (kg · d -1) 1)), there was also a statistically significant difference in urine output (P <0.05). Serum cystatin levels increased with the increase of dose and prolongation of time in the treated group, but serum uric acid concentration gradually decreased with the increase of dose and prolongation of time (P <0.05). Serum creatinine, blood urea nitrogen and serum cystatin C were all increased in the experimental group on the 31st day (P <0.01). Urinary sediment smear drug group found that the specific crystal. The experimental group began to dissect for 31 days and found that the rat kidney started to appear grayish yellow with unclear structure. Many light yellow particles deposited on the junction of the skin and spinal cord to form a yellow arc zone. Some of the kidneys had punctate or patchy hemorrhagic lesions, and many yellowish and translucent concentric circles were found in the pathological sections, mainly in the renal tubules. However, the pathological changes in the 60 mg / kg group were significantly lighter than those in the 200 mg / kg group. Before the time point irrigation group kidney specimens and pathological biopsy were no crystal, only a small amount of pathological section of tubular mild dilatation and tubule epithelial swelling. CONCLUSIONS: Continuous gavage with a dose of melamine cyanurate results in the formation of melamine cyanurate crystals in the kidneys of the rat and impaired glomerular filtration before the formation of crystals, which can clog Tubular damage caused by kidney and even acute renal failure; melamine cyanurate at the same time have a diuretic effect, and can affect the metabolism of uric acid to reduce serum uric acid concentration.