基于代谢组学研究川牛膝对高脂血症慢性血瘀大鼠的保护作用及机制  

Study on Protective Effect and Mechanism of Achyranthes Bidentata on Hyperlipidemia Rats with Chronic Blood Stasis Based on Metabolomics

作　　者：段灿灿 程威纳 王启益 王晓宁 石菊 张建永 DUAN Cancan;CHENG Weina;WANG Qiyi;WANG Xiaoning;SHI Ju;ZHANG Jianyong(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Guizhou Zunyi,563000,China;School of Pharmacy,Zunyi Medical University,Guizhoui Zunyi,563000,China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563000 [2]遵义医科大学药学院,贵州遵义563000

出　　处：《中国中医基础医学杂志》2023年第3期406-412,共7页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81560736)-基于“肝脾同调”研究蓝布正的补血效应及作用机制;贵州省教育厅科技拔尖人才支持项目(黔教合KY字[2017]078)-基于网络药理学和代谢组学的斑蝥肝毒性研究;贵州省中医药、民族医药科学技术研究专项课题(编QZYY2013-95)-基于代谢组学研究牛膝“引血下行”的作用机理。

摘　　要：目的应用代谢组学方法探讨川牛膝治疗高脂血症慢性血瘀大鼠的生物学机制。方法选取健康SD雄性大鼠70只,随机分为正常对照组、模型组、阳性对照组(0.571 g/kg复方丹参片)、川牛膝高剂量组(8 g/kg)、川牛膝低剂量组(2 g/kg),每组14只。采用灌胃脂肪乳(8 mL/kg)结合皮下注射0.01%肾上腺素的方法建立大鼠高脂血症慢性血瘀模型。28 d给药后,处死大鼠,检测全血的血流变参数和血浆中的血脂水平。基于气质联用(gas chromatography-mass spectrometry,GC-MS)的代谢组学技术分析大鼠血浆代谢物,通过数据分析筛选差异代谢物及重要代谢通路。结果川牛膝高剂量组的全血低、中、高切黏度,血液屈服应力,血浆黏度,总胆固醇以及甘油三酯等水平与模型组比较显著降低(P<0.05或P<0.01)。建立的GC-MS代谢组学方法的线性、精密度及重复性等均符合生物样本分析要求。大鼠血浆中7个代谢物的含量(丙酸、L-丝氨酸、肌酸酐、L-苏氨酸、L-谷氨酰胺、半乳糖酸、核糖醇)在川牛膝干预后趋于正常组,这些代谢物主要富集在丙氨酸、天冬氨酸和谷氨酸代谢;氨酰-tRNA(aminoacyl-tRNA)生物合成;甘氨酸、丝氨酸和苏氨酸代谢和甲烷代谢共4条代谢通路。结论川牛膝可改善高脂血症慢性血瘀大鼠的血浆代谢紊乱,其机制与调节丙氨酸、天冬氨酸和谷氨酸代谢等代谢途径有关。Objective This study aims to explore the biological mechanisms of Achyranthes Bidentata on hyperlipidemia rats with chronic blood stasis by the metabonomic method.Methods 70 healthy SD male rats were randomly divided into the normal,model group,Fufang Danshen tablet(0.571 g/kg)and Achyranthes Bidentata high-dose,and low-dose groups(8 g/kg,2 g/kg)(n=14).The model of hyperlipidemia rats with chronic blood stagnation was established by intragastric administration of fat emulsion(8 mL/kg)and subcutaneous injection of 0.01%adrenaline.28 days later,the rats were sacrificed,and the whole blood hemorheological parameters and plasma lipid levels were measured.The differential metabolites and important metabolic pathways in rat plasma were then screened by gas chromatography-mass spectrometry(GC-MS)metabolomic analysis.Results The levels of low,medium and high shear viscosity of whole blood,blood yield stress,plasma viscosity,total cholesterol and triglyceride in Achyranthes Bidentata high dose group was significantly decreased compared with the model group(P<0.05,P<0.01).Moreover,the linearity,precision,and repeatability of the GC-MS metabolomics method met the methodological requirements of biological sample analysis.Finally,the levels of seven differential metabolites(propionic acid,L-serine,creatinine,L-threonine,L-glutamine,galactose acid and adonitol)in plasma tended to the normal group after the intervention of Achyranthes Bidentata,and these metabolites were mainly involved in four metabolic pathways including alanine,aspartate and glutamate metabolism,aminoacyl tRNA biosynthesis,glycine,serine and threonine metabolism,and methane metabolism.Conclusion Achyranthes Bidentata improved the plasma metabolic disorder of hyperlipidemia/chronic blood stagnation rats,and the mechanism was related to alanine,aspartate and glutamate,aminoacyl tRNA biosynthesis,glycine,serine,and threonine metabolism,and methane metabolism.

关 键 词：川牛膝 高脂血症慢性血瘀 代谢组学 GC-MS 代谢通路 

分 类 号：R285.5[医药卫生—中药学]