摘要
目的:基于 1H NMR动态尿液代谢组学技术研究当归—桂枝干预寒凝血瘀证(CCBSS)的动态调控机制.方法:将 15只SD雌性大鼠随机分成正常组、模型组及当桂3∶1组.通过体重变化、血液流变学和纤维蛋白原(FIB)指标评价模型构建成功与否,同时收集各组大鼠不同时间点(第0、第5、第10、第14天)的尿液样本进行 1H NMR代谢组学分析,从代谢层面上阐明CCBSS的发病机制和当归—桂枝干预CCBSS的动态调控机制.结果:与模型组相比,当桂3∶1组大鼠在给予药物干预后其体重降低减缓,FIB指标回调(均P＞0.05),同时血液流变学显著回调(P＜0.01);动态尿液代谢组学结果显示,模型组的代谢轮廓在第5、第10、第14天与正常组明显区分,而当桂3∶1组的代谢轮廓也随着时间的推移逐渐与模型组区分并趋于正常组,基于多元统计分析共筛选出了18种与CCBSS相关的生物标志物,扰动了牛磺酸和低牛磺酸代谢等代谢通路,而当桂3∶1可显著回调这9种生物标志物(乳酸、吡哆醇、琥珀酸、牛磺酸、磷酸肌酸、马尿酸、4-羟基苯乙酸、2-氧戊二酸、柠檬酸)(均P＜0.05),主要干预牛磺酸和低牛磺酸代谢、TCA循环等途径的紊乱.结论:CCBSS的发生发展是一个动态而缓慢的过程,当桂3∶1可通过回调不同时间点的不同代谢物而改善CCBSS.
Abstract
Objective:To explore the dynamic regulatory mechanism of Danggui-Guizhi(DG)intervention on cold coagulation blood stasis syndrome(CCBSS)by employing 1H NMR dynamic urine metabolomics technolo-gy.Methods:Fifteen female SD rats were randomly divided into normal group,model group and DG 3∶1 group.Weight changes,hemorheology,and fibrinogen(FIB)indicators were used to evaluate the success of the model construction.Meanwhile,urine samples were collected from each group of rats at different time points(day 0,day 5,day 10,and day 14)for 1H NMR metabolomics analysis,so as to elucidate the pathogenesis of CCBSS and the dynamic regulatory mechanism of DG intervention on CCBSS at metabolic level.Results:Compared with the model group,the rats in the DG 3∶1 group exhibited a deceleration in weight loss,and FIB indicators under-went a call-back(all P＞0.05)after the DG intervention.Besides,there was a significant call-back in the hemorheological indicators(P＜0.01).The dynamic urine metabolomics analysis revealed that there was a signifi-cant distinction in the metabolic profile between the model group and the normal group on days 5,10,and 14,and the metabolic profile of the DG 3∶1 group was gradually separated from the model group and then ap-proached the normal group as time progressed.Based on multivariate statistical analysis,a total of 18 biomarkers associated with CCBSS were identified,which involved metabolic pathways including taurine and hypotaurine metabolism.The DG 3∶1 group could call back the disorder of these 9 biomarkers(lactate,pyridoxine,succinate,taurine,creatine phosphate,hippurate,4-hydroxyphenylacetate,2-oxoglutarate,citrate)(all P＜0.05),which mainly interfered with the disorders of taurine and hypotaurine metabolism,as well as TCA cycle and other pathways.Conclusion:The occurrence and development of CCBSS is a dynamic and slow process,and DG 3∶1 can improve this syndrome by calling back various metabolites at different time points.
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