目的分析肝豆灵对铜负荷大鼠肾损伤的代谢组学影响,探讨肝豆灵的肾脏排铜机制。方法实验大鼠被随机分为正常组、模型组和肝豆灵组。造模结束后,以TUNEL法测肾小管上皮细胞凋亡,核磁共振技术结合偏最小二乘判别分析法分析大鼠肾组织小分子代谢物。结果与正常组比较,模型组肾小管上皮细胞凋亡指数升高(P〈0.01);苯丙氨酸、丙氨酸、酪氨酸、谷氨酸、赖氨酸、缬氨酸、亮氨酸、肌苷、天冬氨酸含量降低。与模型组相比,肝豆灵组肾小管上皮细胞凋亡指数降低(P〈0.01);苯丙氨酸、丙氨酸、酪氨酸、谷氨酸、赖氨酸、缬氨酸、亮氨酸、肌苷、天冬氨酸含量升高。结论肝豆灵对铜负荷大鼠肾损伤具有一定的干预作用,其机制可能涉及对芳香族氨基酸(苯丙氨酸、酪氨酸)、支链氨基酸(亮氨酸、缬氨酸)的调节;抑制肾小管上皮细胞凋亡、调节肾脏氨的代谢。
Objective To explore the influences of Gandouling on liver injury of copper-laden rats. Methods The tested rats were randomly divided into the control group, model group and Gandouling group. After modeling, TUNEL method was applied to test the apoptosis cells index and NMR-based metabonomics was applied to analyze the metabolic changes of rat kidney tissue. Results Compared with the control group, the apoptosis cells index in kidney of the model group was significantly increased (P〈 0.01 ); the content of phenylalanine, alanine, tyrosine, glutamate, lysine, valine, leucine, inosine and aspartate was decreased. Compared with the model group, the apoptosis ceils index in kidney of the Gandouling group was significantly decreased (P〈0.01); the content of the above metabonolates was increased. Conclusion There is certain intervention influence of Gandouling on copper- laden rats. The related mechanism may involve regulating aromatic amino acid (phenylalanine, alanine) and branched chain amino acid(valine, leucine ) metabolism, inhibiting apoptosis of renal tubule epithelia and regulating ammonia metabolism.