三聚氰胺肾毒性研究

Kidney Damage Induced by Melamine

目的探讨三聚氰胺致大鼠肾毒性的致病机制及病变特点。方法将清洁级Wistar大鼠20只随机分为三聚氰胺染毒组[饲料中三聚氰胺含量为250mg/kg,染毒剂量为25mg(/kg·d)]和对照组(饲料中不加三聚氰胺),染毒4周后取血清测定生化指标;肾脏切片,于解剖镜下观察形态学变化;肾脏称重,计算肾/体比值;并进行肾脏组织病理学检查;采用液相色谱-质谱联用技术测定肾脏三聚氰胺和三聚氰酸含量;以X射线衍射法确定肾脏结晶体化学结构。结果大鼠喂饲含有三聚氰胺的饲料4周后出现多尿,少动,体重下降,血清肌酐、尿素氮、甘油三酯增高,肾脏外观明显改变,解剖镜下观察肾脏切片可见弥漫性分布的点片状晶体阴影。组织病理检查可见肾小管中存在大量晶体,肾小管上皮受损。X射线衍射法确认肾脏中含有三聚氰胺和三聚氰酸的结合。肾脏内的晶体经液相色谱-质谱联用检测含有三聚氰胺和三聚氰酸。结论三聚氰胺经消化道进入体内能部分水解生成三聚氰酸,两者在肾脏结合生成三聚氰胺-三聚氰酸结合晶体。晶体阻塞肾小管并造成肾小管上皮细胞损伤可导致肾小管重吸收功能障碍,最终导致肾功能衰竭。

Objective To explore the pathogenesis of renal damage induced by melamine and the characteristics of kidney damage in rats. Methods Twenty Wister rats were randomly divided into one control group fed with normal pet food and one exposure group fed with animal food mixed with melamine at 25 mg/（kg ·d）. After 4 weeks, biochemical indexes of blood were determined, histopathological examination was performed, and kidney/body weight was measured among rats. The kidney slices were observed using light microscopy of animal anatomy. Renal tissues from affected rats were analyzed using high-performance liquid chromatography and mass spectrometry. Kidney X-ray diffraction were performed to determine the existence of crystals Results After 4 weeks of melamine exposure, the rats showed polyuria , less activity, weight loss, increasing levels of serum creatinine, urea nitrogen, triglyceride. The appearance of kidney significantly changed. The diffuse distribution of the point and the flake crystal shadow were observed in kidney slices. Histopathological examination showed the existence of a large number of crystals in renal tubular, renal tubular epithelial damage. The analysis of high-performance liquid chromatography and mass spectrometry revealed that crystals were composed of melamine and cyanuric acid. Kidney X-ray diffraction revealed that crystals could be found in kidneys of rats. Conclusion Melamine can enter the body through the digestive tract and generate partially cyanuric acid through hydrolysis. Then cyanuric acid and melamine formed eocrystals in renal tubules leading to progressive tubular blockage, renal tubular epithelial damage, tubular reabsorption dysfunction, eventually renal failure.