金威消石颗粒抑制豚鼠胆固醇胆石形成的代谢组学研究

The Research into Metabolomics of Cholesterol Gallstone Formation in Guinea Pigs Inhibited by Jinwei Xiaoshi Particles

目的:采用1H核磁共振(1H NMR)代谢组学技术研究胆固醇胆石豚鼠血清的特征性代谢物及金威消石颗粒抑制胆固醇胆石形成的机制。方法:将45只健康成年雄性豚鼠随机分为模型组、中药组和对照组,模型组和中药组服用致石饲料15周,对照组服用常规饲料15周,中药组第8周开始以金威消石颗粒混悬液灌胃8周,2.65 g·kg-1,每天2次。第16周第1天清晨采集所有豚鼠空腹腹腔动脉血1 m L,摘取胆囊收集胆汁,观察胆石形成情况;采用1H NMR技术检测血清小分子代谢物。结果:金威消石颗粒可明显抑制豚鼠胆固醇胆石的形成。与对照组相比,模型组血清柠檬酸、丙酮、谷氨酸、甘氨酸、赖氨酸、蛋氨酸、苯丙氨酸和酪氨酸等含量明显升高(P<0.05),乳酸、丙酮酸和谷氨酰胺明显降低(P<0.05)。与模型组相比,中药组血清1-甲基组氨酸含量明显增高,丙酮和组氨酸含量下降(P<0.05)。结论:豚鼠胆固醇胆石的形成与能量、脂类及蛋白质代谢紊乱有关,金威消石颗粒可通过调整豚鼠脂类和蛋白质代谢抑制胆固醇胆石的形成。

Objective： To adopt 1H NMR metabolomics technology to research into special metabolites of guinea pig serum with cholesterol gallstone,and the mechanism of Jinwei Xiaoshi Particles（ JWXSP） in inhibiting cholesterol gallstone formation. Methods： Forty-five healthy adult male guinea pigs were randomly divided into the model group,the TCM group and the control group.The ones in the model group and the TCM group took the feed leading to gallstones for 15 weeks,while the ones in the control group took the routine feed for 15 weeks. From the 8th week,the ones in the TCM group were given JWXSP for intra-gastric administration suspension or intra-gastric administration for 8 weeks,2. 65 g / kg each time,2 times a day. On the early morning of the first day of the 16 th week,1 m L of blood of all guinea pigs’ celiac artery in an empty stomach were was observed; 1H NMR technology was used to detect small-molecule metabolites in serum. Results： JWXSP could obviously inhibit cholesterol gallstone formation of guinea pigs. Compared with the control group,citric acid,pyruvic acid,glutamic acid,glycine,lysine,methionine,phenylalanine and tyrosine contents of blood serum in the model group increased significantly（ P 〈 0. 05）,but its lactic acid,pyruvic acid and glutamine decreased significantly（ P 〈 0. 05）,which showed that there were serious disorder of energy,fat and protein metabolism in the model group. Compared with the model group,serum Methyl-Histidine content of the TCM group increased significantly,but acetone and Histidine content decreased（ P 〈 0. 05）. Conclusion： The formation of cholesterol gallstones of guinea pigs has something to do with disorder of energy,fat and protein metabolism. JWXSP can obviously inhibit cholesterol gallstone formation by regulating fat and protein metabolism.