雷公藤红素对炎症性肠病小鼠血清中胆汁酸代谢谱的影响

Effects of celastrol on serum bile acid metabolite profiling in mice with inflammatory bowel disease

目的:通过研究雷公藤红素对炎症性肠病(inflammatory bowel disease,IBD)模型小鼠血清中胆汁酸代谢谱的影响,探究雷公藤红素干预IBD的可能机制。方法:用葡聚糖硫酸钠诱导IBD小鼠模型,采用色谱-串联质谱技术,测定IBD小鼠血清中22种胆汁酸的含量。结果:IBD小鼠血清中胆酸(CA)、鹅去氧胆酸(CDCA)等游离型初级胆汁酸的相对含量显著升高,而牛磺胆酸(TCA)、牛磺去氧胆酸(TDCA)等结合型初级胆汁酸的相对含量明显降低,石胆酸(LCA)等次级胆汁酸的相对含量显著降低。给予雷公藤红素后,IBD小鼠血清中上述初级和次级胆汁酸的代谢趋势均有所恢复。结论:雷公藤红素可能调节了IBD小鼠肝脏功能及其中相关代谢酶的表达,干预了结合型胆汁酸的合成过程,从而改善IBD小鼠的症状。

Objective:To explore the potential mechanism of celastrol in inflammatory bowel disease(IBD)by investigating its effects on the serum bile acid metabolite profiling of IBD mice.Methods:The IBD mice model was developed by using dextran sulfate sodium.The relative concentrations of22bile acids in the serum of IBD mice were determined by using UPLC-MS/MS.Results:In IBD mice,the relative concentrations of free primary bile acids,such as cholic acid(CA)and chenodeoxycholic acid(CDCA)were significantly increased,while the levels of several binding primary bile acids,such as taurocholic acid(TCA)and taurodeoxycholic acid(TDCA)were obviously decreased,and the levels of some secondary bile acids,such as lithocholic acid(LCA)were also significantly reduced.After administration of celastrol,the metabolic changes of the above primary and secondary bile acids in the serum of the IBD mice recovered to a certain extent.Conclusion:Celastrol might regulate the liver function and metabolic enzyme expression of the IBD mice,intervene the binding process of primary bile acids,thus improve the symptoms of the IBD mice.