逍遥散对肝郁脾虚证和肝损伤模型大鼠干预作用的代谢组学研究

Metabonomics study on the intervention of Xiaoyao powder on the rates with model of liver depression and spleen deficiency patterns and liver disease

目的：利用代谢组学方法探讨肝郁脾虚证和肝损伤模型的共同本质及逍遥散的干预作用。方法将40只SD大鼠按随机数字表法分为空白对照组、肝郁脾虚证模型组、肝郁脾虚证给药组、肝损伤模型组、肝损伤给药组，每组8只。采用夹尾激怒致肝郁联合番泻叶致脾虚的方法制备肝郁脾虚证模型，采用四氯化碳致肝损伤法制备肝损伤大鼠模型。肝郁脾虚证给药组、肝损伤给药组灌胃2 g/ml逍遥散液，其余各组灌胃等体积生理盐水，连续给药28 d。末次给药后12 h，采用气相色谱-质谱法分析各组大鼠血清代谢物谱及含量变化，采用 HE 染色法观察各组大鼠肝组织病理学变化。结果肝郁脾虚证模型组和肝损伤模型组大鼠肝组织均出现细胞核萎缩、崩解、变性坏死并伴有淋巴细胞浸润等病理改变，且血清中甘氨酸、琥珀酸、丙酸、蛋氨酸、谷氨酰胺、苯丙氨酸含量较空白对照组升高（P＜0.05）。逍遥散可降低血清中甘氨酸、琥珀酸、丙酸、蛋氨酸、谷氨酰胺、苯丙氨酸含量（P＜0.05）。结论逍遥散可调节一碳单位、含硫氨基酸、芳香族氨基酸等特殊代谢及三羧酸循环，发挥肝保护作用。

Objective To discuss the common nature of live depression and spleen qi deficiency and liver disease and the changes after the intervention ofXiaoyaopower by the metabonomics method. Methods A total of 40 rats were randomly devided into the normal control group, the liver depression and spleen qi deficiency model group, the liver depression and spleen qi deficiency treatment group, the liver disease group, the liver disease treatment group, 8 in each group. The liver depression and spleen qi deficiency model rat was established by tail-clamping infuriation and Senna gavage method, and the liver disease model rat was established by the CCl4-induced liver injury method. The rats of the liver depression and spleen qi deficiency treatment group and the liver disease treatment group were given 2 g/mlXiaoyao powder, and other groups were given the equal-volume saline. All the treatment lasted 28 days. Twelve hours after the last administration, rat metabolite profiling and contents in the serum were detected by GC-MS, the change of rat liver tissue was observed through HE staining.Results The rats of liver depression and spleen deficiency pattern and liver disease model group appeared liver cell nuclei atrophy, dissolution, degeneration necrosis and lymphocyte infiltration, and at the same time the contents of Glycine, Butanediodic acid, Propanoic acid, Methionine, Glutamine, Phenylalanine in serum were all higher than the normal control group （P〈0.05）. AndXiaoyao powder could reduce the content of the contents of Glycine, Butanediodic acid, Propanoic acid, Methionine,Glutamine, Phenylalanine in serum （P〈0.05）.ConclusionXiaoyao powder may play the role of protecting liver by the regulation of one carbon unit, sulfur containing amino acids, aromatic amino acids and amino acid of special metabolism and three tricarboxylic acid cycle.