疏肝健脾方对CCl4诱导的肝纤维化大鼠尿液代谢组学的影响

Effects of Shugan Jianpi Formula on urine metabonomic in rats with hepatic fibrosis induced by CCl_4

目的观察疏肝健脾方(茵陈、柴胡、黄芪、白芍、枳壳、白术、猪苓、茯苓、泽兰)对肝纤维化大鼠尿液代谢谱的影响并推测其作用机制。方法皮下注射50%CCl4橄榄油溶液诱导肝纤维化的SD大鼠随机分为模型组和疏肝健脾方组,并设正常组,连续给药12周后,收集大鼠尿液,用GC-TOF/MS技术结合主成分分析、偏最小二乘方-判别模式、正交偏最小二乘方-判别模式法鉴定其代谢谱化合物变化。结果模型组中的2-羟基丁酸、异亮氨酸、beta-丙氨酸、氨基丙二酸、胞嘧啶、赖氨酸与正常组相比含有量显著升高,疏肝健脾方能够使6个生物标志物向正常水平靠近。结论疏肝健脾方对化学性肝纤维化大鼠有一定的保护作用,其机制可能与调节能量代谢、嘧啶合成代谢、氨基酸代谢有关。

AIM To study the metabolic changes of Shugan Jianpi Formula（ Artemisiae scopariae Herba,Bupleuri Radix,Astragali Radix,Paeoniae Radix alba,Aurantii Fructus,Atractylodis macrocephalae Rhizoma,Polyporus,Poria, Lycopi Herba） on experimental liver fibrosis in rats and to explore its possible mechanisms.METHODS The rats with liver fibrosis were induced by subcutaneous injection of 50% carbon tetrachloride-olive oil solution. They were assigned to the model group and Shugan Jianpi Formula group. Some other rats were selected as health control group. All groups were given lavage for twelve weeks. The metabolic profile changes of urine samples were analyzed by GC / TOFMS and the results were processed by principal component analysis,partial least squares-discriminate analysis,and orthogonal projections to latent structures discriminant analysis. RESULTS Compared with the control group,six significantly changed metabolites,such as 2-hydroxybutanoic acid,isoleucine,beta-alanine acid,cytidine,lysine were identified. As compared with the model group,Shugan Jianpi Formula group could reverse the levels of these metabolites to normal or close to normal levels. CONCLUSION The current study indicates that Shugan Jianpi Formula has significant anti-fibrotic effects on CCl4-induced liver fibrosis in rats,which might be related to regulating the dysfunction of energy metabolism,pyrimidine metabolism and amino acid metabolism.