在 CCl 诱导的急性肝损伤中的代谢组学及其对大鼠胆汁酸谱的调节作用。

Metabolomics of in CCl induced acute liver injury and its regulatory effect on bile acid profile in rats.

机构信息

The Second Department of General Surgery, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China.

Department of Educational Administration, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, Liaoning Province, China.

出版信息

World J Gastroenterol. 2021 Oct 28;27(40):6888-6907. doi: 10.3748/wjg.v27.i40.6888.

BACKGROUND

( lateralis)- () is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure.

AIM

To investigate the metabolomics of F-G in CCl induced acute liver injury in rats and its regulatory effect on the bile acid profile.

METHODS

The pharmacodynamic effect of F-G on CCl induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver.

RESULTS

Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group.

CONCLUSION

F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.

背景

（白芍）是中药最经典的药对之一。在临床实践中，含有（白芍）的方剂常被用于治疗肝炎和肝衰竭等肝脏疾病。

目的

研究 F-G 对 CCl4 诱导的急性肝损伤大鼠的代谢组学及对胆汁酸谱的调节作用。

方法

评价 F-G 对 CCl4 诱导的急性肝损伤大鼠的药效作用，建立同时测定 92 种来自多个途径的代谢物的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，以探讨 F-G 在血清中对肝脏的保护代谢机制。

结果

在血清样品中鉴定出 24 个差异代谢物。初级胆汁酸生物合成代谢途径是模型组和 F-G 组的主要共同途径。随后，建立了一种 UPLC-MS/MS 方法，用于同时测定 11 种胆汁酸，包括胆酸、熊去氧胆酸、甘氨胆酸、甘氨脱氧胆酸、牛磺胆酸、甘胆酸、鹅脱氧胆酸、脱氧胆酸、牛磺鹅脱氧胆酸、牛磺胆酸和甘氨酸，以分析 F-G 在血清中的调节机制。与模型对照组相比，F-G 呈剂量依赖性降低了这些 11 种胆汁酸在血清中的含量。