昆仙胶囊对MRL/lpr小鼠狼疮性肾炎的代谢组学研究

Metabonomics study of Kunxian capsule on MRL/lpr mice of lupus nephritis

目的:探讨昆仙胶囊对MRL/lpr小鼠狼疮性肾炎的影响及作用机理。方法:MRL/lpr小鼠随机分为模型对照组、昆仙胶囊组、来氟米特组,各组均连续用药4周。分别于给药前,给药结束后采集小鼠清晨空腹尿液与血清。考马斯亮蓝G250法检测尿蛋白浓度,ELISA法测定血清抗ANA抗体及抗ds-DNA抗体,基于1HNMR的代谢组学方法分析给药后各组小鼠尿液的代谢特征。结果:昆仙胶囊组按照234mg/kg剂量给药后,与模型组比较,小鼠尿蛋白浓度,血清抗ANA抗体及抗ds-DNA抗体水平显著降低;并且尿液中乳酸、TMAO、柠檬酸、葡萄糖、谷氨酰胺、丙氨酸降低,а-酮戊二酸、肌酸/肌酐、马尿酸盐升高。结论:昆仙胶囊可以显著改善MRL/lpr小鼠的免疫状况和肾脏功能,该研究结果为临床治疗LN提供了实验基础。

Objective： To study on the effect of Kunxian Capsule on lupus nephritis in MRL/lpr lupus mice.Methods： MRL/lpr lupus mice were randomly divided into three groups： model group,Kunxian capsule group and Leflunomide tablets group.The administration of the drugs lasted for 4 weeks,and the urine and serum of the mice were collected before and after the administration.Proteinuria was detected by Comarssie brilliant blue G250 method,and the level of serum anti-ANA antibody and anti-ds-DNA antibody was assayed by ELISA.After 4 weeks of drug administration,metabonomic study of the urine on mice based on 1H NMR were carried out.Results： Compared with model group,the levels of urinary protein concentration,anti-ANA antibody and anti-ds-DNA antibody in mice treated by Kunxian capsule according to 234mg/kg,decreased significantly.But the differences between Kunxian capsule group and Leflunomide tablets group were not significant.The metabonomic study showed that,the lactate,TMAO,citrate,glucose,glutamine and alanine in the urine of Kunxian capsule group were lower than that of model group,while the а-oxoglutarate,creatine/creatinine and hippurate in the urine of Kunxian capsule group increased.Conclusion： Kunxian capsule may improve immune status and renal function of MRL/lpr lupus mice.This study may provide experimental evidence for the therapy of LN.