基于胆汁酸代谢谱对自身免疫性肝炎小鼠模型的早期预判研究

Pre-identification of autoimmune hepatitis mice model by bile acids profiles

目的:采用液相色谱质谱联用仪(LC-MS/MS)测定胆汁酸代谢谱的分析方法评价刀豆蛋白A诱导自身免疫性肝炎(autoimmune hepatitis,AIH)小鼠模型。方法:小鼠经30 mg·kg^(-1)刀豆蛋白A诱导后可成功建立AIH模型(可称为模型组);而经20 mg·kg^(-1)刀豆蛋白A诱导后其生化、病理指标均未发生显著变化(可称为模型前组)。结果:通过血清胆汁酸谱分析发现模型前组小鼠有部分胆汁酸成分明显升高,而模型组小鼠所有胆汁酸成分均急剧升高。进一步经主成分分析及正交-偏最小二乘法判别分析后证明胆汁酸谱即可对模型前组小鼠与正常组小鼠做出明显区分,并从中筛选出能够提前进行亚疾病状态预判的潜在生物标志物。结论:本文为临床AIH患者的早期诊断及病程分级研究奠定了基础。

Obejective:To evaluate autoimmune hepatitis(AIH)mice model induced by concanavalin A(ConA)through determination of metabolic profile of bile acids using LC-MS/MS.Methods:The AIH mice models were successfully induced by 30 mg·kg^(-1) ConA(model group).The biochemical and pathological mechanisms were not changed in the models induced by 20 mg·kg^(-1) ConA(pre-model group).Results:By analysis of serum bile acids profile,a part of the components in bile acids increased in pre-model group,and all of the components in bile acids increased significantly.By using the principle components analysis(PCA)and orthogonal projections to latent structures discriminant analysis(OPLS-DA),bile acids profile could differentiate pre-model group mice from control group mice,and could screen the biomarkers which could pre-identification the Sub-diseases.Conclusion:This work can provide the base for study of the early clinical diagnosis and grading the course of disease in the patients with AIH.