阿托伐他汀联合臻通集胶囊治疗高脂血症模型大鼠的代谢组学研究

Metabonomics study of atorvastatin combined with Zhentongji capsule on hyperlipidemia model of rats

  • 摘要: 目的:基于代谢组学探究阿托伐他汀联合臻通集胶囊治疗高脂血症模型大鼠的疗效和作用机制。方法:SD大鼠随机取6 只作为对照组,正常饮食、饮水。其余动物均给予高脂饲料,连续4 周后,甘油三酯(TG)和胆固醇(CHO)明显升高视为模型成功;根据CHO水平进行分组,分为模型组、西药组(阿托伐他汀钙片,0.9 mg/kg)、中药组(臻通集胶囊,0.216 g/kg)、中西医联合组(二者联用)。连续给药8周后,检测各组动物血清中的血脂水平,肝脏组织用于高分辨非靶代谢组学的研究。结果:模型组TG、CHO、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平较对照组显著升高(P< 0.05);与模型组相比,西药组、中药组和中西医联合组血脂水平显著降低(P< 0.05);与对照组相比,模型组共检测出138个差异代谢物;与模型组相比,西药组共检测出64 个差异代谢物,中药组共检测出123 个差异代谢物,中西医联合组共检出106 个差异代谢物;中药组与西药组相比,共检出101 个差异代谢物;经相关性分析和KEGG 通路分析,主要涉及衰老、脂质代谢、氨基酸代谢、膜转运等通路。结论:阿托伐他汀联合臻通集胶囊能够有效地改善高血脂大鼠的血脂水平,代谢组学分析示其可能通过调节cGMP-PKG 信号通路相关因子的表达,达到抑制肝脏细胞坏死的目的。

     

    Abstract: Objective: To explore the therapeutic effect and mechanism of atorvastatin combined with Zhenton-gji capsule on hyperlipidemia model rats through metabonomics.Methods: Six SD rats were randomly selected as the control group, and they were given normal diet and water.The other animals were given high-fat feed, and after 4 weeks, triglyceride(TG)and cholesterol(CHO)increased significantly, which was regarded as the success of the model.According to CHO index, they were divided into model group, western medicine group (atorvas-tatin calcium tablet, 0.9 mg/kg), traditional Chinese medicine group(Zhentongji capsule, 0.216 g/kg)and integrat-ed traditional Chinese and western medicine group (both combined).After 8 weeks of continuous administration, the serum lipid levels of animals in each group were detected, and the liver tissue was used for high-resolution un-targeted metabolomics research.Results: The levels of TG, CHO, high density lipoprotein (HDL)and low densi-ty lipoprotein (LDL) in the model group were significantly higher than those in the control group (P< 0.05).Compared with the model group, the blood lipid lev-els in the western medicine group, the traditional Chinese medicine group and the integrated tradition-al Chinese and western medicine group significantly reduced (P< 0.05).Compared with the control group, 138 different metabolites were detected in the model group.Compared with the model group, 64 different metabolites were detected in the western medicine group, 123 in the traditional Chinese medicine group and 106 in the integrated traditional Chinese and western medicine group.Compared with the western med-icine group, 101 different metabolites were detected in the traditional Chinese medicine group.Through correla-tion analysis and KEGG pathway analysis, it was mainly involved aging, lipid metabolism, amino acid metabo-lism, membrane transport and other pathways.Conclusion: Atorvastatin combined with Zhentongji capsule can effectively improve the blood lipid levels of hyperlipidemia rats.Metabolomics analysis shows that it may achieve the purpose of inhibiting liver cell necrosis by regulating the expression of related factors in cGMP-PKG signaling pathway.

     

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