1. 上海中医药大学科技实验中心,上海,201203
2. 上海市宝山区中西医结合医院中心实验室,上海,201999
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赵鑫, 苟小军, 陈龙, 等. 花旗松素预防CCl4致大鼠急性肝损伤的代谢组学研究[J]. 上海中医药杂志, 2017,51(8):82-86.
ZHAO Xin, GOU Xiao-jun, CHEN Long, et al. Metabonomic study of the preventive effects of taxifolin on CCl4-induced acute liver injury in rats[J]. Shanghai Journal of Traditional Chinese Medicine, 2017,51(8):82-86.
目的:从代谢组学的角度探讨预防给药花旗松素对CCl,4,造成的大鼠急性肝损伤的保护作用及其可能的作用机制。 方法:Wistar大鼠30只,随机分为正常组、模型组和花旗松素组,每组10只。正常组和模型组灌胃给予浓度为0.5 %的CMC-Na溶液,花旗松素组每天灌胃给予含花旗松素(150 μg/g)的CMC-Na溶液,连续灌胃给药14天。末次给药后2 h,模型组和花旗松素组腹腔注射CCl,4,造成大鼠急性肝损伤,造模后24 h取血及肝脏,计算肝指数,测定大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST),测定大鼠肝组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,并进行病理组织学观察,采用液相色谱质谱联用技术(LC/MS)分析其代谢谱变化,并鉴定差异性代谢物。 结果:与正常组比较,模型组大鼠的肝指数增加(P,<,0.01),ALT、AST增高(P,<,0.01),SOD活性降低(P,<,0.01),MDA水平增高(P,<,0.05),肝组织的损伤明显。与模型组比较,花旗松素组肝指数降低(P,<,0.01), ALT、AST水平降低(P,<,0.01),SOD活性升高、MDA水平降低(P,<,0.05),肝组织的损伤程度减轻。与正常组比较,模型组中存在差异性代谢物12种:牛磺胆酸、胆酸、去氧胆酸、苏氨酸、焦谷氨酸、谷氨酸盐、PE(16∶0)、二十二碳五烯酸、PE(18∶1)、PE(18∶2)、PS(18∶1)和PS(18∶2),给药花旗松素后这些差异性代谢物有回调趋势。 结论:花旗松素对CCl,4,造成的化学性肝损伤具有保护作用,其机制可能与抗脂质过氧化,调节胆汁酸代谢、氨基酸代谢、脂肪酸代谢和甘油磷脂代谢紊乱有关。
Objective:To investigate the preventive effects of taxifolin on CCl,4,-induced acute liver injury in rats and its possible mechanism based on metabonomic. Methods A total of 30 Wistar rats were randomly divided into the normal group,model group and taxifolin group,10 rats in each group. The normal group and model group were treated with 0.5% CMC-Na solution for intragastric administration,and the taxifolin group was treated with taxifolin at daily dose of 150 μg/g for intragastric administration,with a course of continuous 14 days. 2 hours after the last administration, the model group and taxifolin group were treated with CCl,4, for intraperitoneal injection to induce the acute liver injury. 24 hours after modeling,the blood and liver tissue were collected and the liver index was calculated. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST),the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in liver tissue were detected,and the histopathological changes of liver were observed. The changes of metabolic spectrum were analyzed by liquid chromatography-mass spectrometry (LC/MS), and the differential metabolites were identified. Results: Compared with the normal group,the liver index was increased in the model group(P,<,0.01),and the levels of ALT and AST were increased(P,<,0.01),the activity of SOD was decreased(P,<,0.01)and the content of MDA was increased(P,<,0.05),the obvious liver injury was observed. Compared with the model group,the liver index was decreased in the taxifolin group(P,<,0.01),and the levels of ALT and AST were decreased(P,<,0.01),the activity of SOD was increased and the content of MDA was decreased(P,<,0.05),the damage degree of liver tissue was improved. Compared with the normal group,there were 12 kinds of differential metabolites in the model group,including taurocholic acid,cholic acid,deoxycholic acid,threonine,pyroglutamic acid,glutamine,phosphatidyl ethanolamine(PE)(16:0),docosapentenoic acid,PE(18:1),PE(18:2),phosphatidyl serine(PS)(18:1) and PS(18:2). After the treatment with taxifolin,these metabolites showed the callback trend. Conclusion: Taxifolin shows protective effects on CCl,4,-induced chemical liver injury,its mechanism may be associated with inhibition of lipid peroxidation and regulation of bile acid metabolism,amino acid metabolism,fatty acid metabolism and glycerol phospholipid metabolism disorder.
大鼠花旗松素四氯化碳肝损伤代谢组学液相色谱质谱联用
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