应用蛋白质组学技术探讨诃子醇提物诱导小鼠肝毒性机制

Study on the mechanism of hepatotoxicity in mice induced by terminalia chebula extract with proteomics

目的:利用蛋白质组学技术研究诃子醇提物对小鼠肝脏毒性的作用机制。方法:采用二维凝胶电泳分离肝脏蛋白样品,以飞行时间质谱、生物信息学分析等方法鉴定各差异表达蛋白。结果:诃子醇提物给药组共鉴定出18个明显变化的肝脏差异表达蛋白,其中10个蛋白表达明显上调,分别为细胞色素b5、二氢喋啶还原酶、钙调素、硫代硫酸硫转移酶、40S核糖体蛋白SA、乙酰辅酶A乙酰基转移酶、钙网蛋白、电压依赖性阴离子选择性通道蛋白1、NADH脱氢酶复合体、氨甲酰磷酸合成酶;表达明显下调的8个蛋白分别是乳酰谷胱甘肽裂合酶(乙二醛酶)、甘氨酸-N-酰基转移酶样蛋白、原肌球蛋白3、苹果酸脱氢酶、ATP合成酶α亚基、甜菜碱高半胱氨酸甲基转移酶1、延胡索二酰乙酰乙酸酶、烟酸磷酸核糖转移酶。结论:这些蛋白表达的改变提示诃子醇提物诱导小鼠肝毒性作用与脂类代谢、线粒体损伤、能量代谢紊乱、氨基酸代谢异常有关。

Objective： To explore the mechanism of hepatotoxicity in mice induced by terminalia chebula extract with proteomics. Methods： Protein samples were separated by two-dimensional gel electrophoresis and identified differential proteins by the method of flight time and bioinformatics analysis. Results： Terminalia chebula administration group identified 18 differential proteins in liver, of which 10 proteins＇ expressions were significantly up-regulated respectively, including cytochrome b5, dihydro peridine reductase（DHPR）, calmodulin, thiosulfate sulfurtransferase（TST）, 40 S ribosomal protein SA, acetyl-Co A acetyltransferase（ACAT）, calreticulin, voltage-dependentanion channels 1（VDAC1）, NADH dehydrogenase complex, carbamoyl phosphate synthetase（CPS）, and the expressions of 8 proteins were significantly down-regulated including lactoyl glutathione lyase（glyoxalase）, glycine-N-acyltransferase-like protein, tropomyosin 3, malate dehydrogenase（Mdh1）, ATP synthase asubunit, high betaine homocysteine methyltransferase 1（BHMT1）, fumaric acid dihydrazide acetyl enzyme（FAA）, Nicotinic acid phosphoribosyltransferase（NAPRT）. Conclusion： The mechanism of hepatotoxicity in mice induced by terminalia chebula extract with proteomics might be associated with the lipid metabolism, mitochondrial damage, energy metabolism, and amino acid metabolism abnormalities.