二乙基亚硝胺对大鼠肾代谢通路的影响

Effect of diethylnitrosamine on renal metabolic pathway in rats

目的:探讨与二乙基亚硝胺(diethyl nitrosamine,DEN)肾毒性有关的肾代谢标志物及其参与的代谢通路。方法:将19只大鼠随机分为两组:健康对照组(n=9),给予大鼠灭菌食用水自由饮用;DEN给药组(n=10),给予大鼠0.1mg/mLDEN溶液自由饮用。18周后麻醉并处死大鼠采集肾组织进行磁共振代谢组学检测和病理学检测。结果:与健康对照组比较DEN给药组大鼠肾代谢物的含量变化比较明显,如丙氨酸、牛磺酸、醋酸盐、丙酮酸、胆碱含量显著减少,而肌酸、甘氨酸、氧化三甲胺、蛋氨酸、脯氨酸、乳酸、缬氨酸、亮氨酸、异亮氨酸含量显著增加。结论:DEN给药组大鼠肾组织有5种代谢通路发生了明显的变化,包括缬氨酸、亮氨酸、异亮氨酸生物合成通路,甘氨酸,丝氨酸和苏氨酸代谢通路,丙酮酸代谢通路,糖酵解和糖异生通路及半胱氨酸和蛋氨酸代谢通路。

Objective:To explore the renal metabolic markers relavant to the renal toxicity of diethylnitrosamine and the metabolic pathways involved in the renal metabolic markers. Methods:Nineteen Sprague Dawley rats were assigned into 2 groups:A normal control group (n=9) and a diethylnitrosamine (DEN) administration group (n=10).The rats in the normal control group were given sterilized water for free drinking.The rats in the DEN administration group were given 0.1 mg/mL DEN solution for free drinking.After 18 weeks,the kidney tissues were collected and tested for nuclear magnetic resonance detection and pathological examination. Results:The content of kidneys metabolites in the rats with the DEN administration was changed significantly.The levels of alanine,taurine,pyruvate,acetate,and choline were significantly reduced compared with rat in the normal control group,while the levels of creatine,glycine,TMAO, methionine,proline,lactate,valine,leucine and isoleucine were significantly increased. Conclusion:Metabolicomics studies have revealed significant differences in five metabolic pathways,including valine,leucine and isoleucine biosynthesis,glycine serine and threonine metabolism,pyruvate metabolism,glycolysis or gluconeogenesis,cysteine and methionine metabolism.