葛根芩连汤干预高脂血症肥胖大鼠的粪便代谢组学研究  

Fecal Metabolics Study of Gegen Qinlian Decoction in Obese Rats with Hyperlipidemia

作　　者：姚亮亮[1] 盛译萱 曾国威 周子妍 曾治君[1,2] 李冰涛 姜丽[1,2] 徐国良 Yao Liangliang;Sheng Yixuan;Zeng Guowei;Zhou Ziyan;Zeng Zhijun;Li Bingtao;Jiang Li;Xu Guoliang(Research Center for Differentiation and Development of Traditional Chinese Medicine(TCM)Basic Theory,Nanchang 330004;Jiangxi Key Laboratory of TCM Etiopa-thogenesis,Nanchang 330004;Jiangxi Key Laboratory of Pharmacology of TCM,Nanchang 330004;Guangzhou First Peopled Hospital,Guangzhou 510180)

机构地区：[1]江西中医药大学中医基础理论分化发展研究中心,南昌330004 [2]江西省中医病因学重点实验室,南昌330004 [3]江西省中药药理重点实验室,南昌330004 [4]广州市第一人民医院,广州510180

出　　处：《中药药理与临床》2020年第3期47-52,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金资助项目(编号:81560744、编号:81760787);江西省自然科学基金项目(编号:20192BAB205094);江西省中药学一流学科专项科研基金项目(编号:JXSYLXK-ZHYAO117、 JXSYLXK-ZHYAO063)。

摘　　要：目的:探讨葛根芩连汤干预高脂血症肥胖大鼠肠道代谢,改善脂代谢的相关代谢机制。方法:将大鼠随机分成正常对照组与高脂组,高脂组以高脂饲料饲养建立高脂血症肥胖大鼠模型,待模型建立后,将高脂组大鼠随机分为模型对照组,葛根芩连汤14.85 g/kg、4.85 g/kg、1.65 g/kg组,各组继续给予高脂饲料并给药7 w,观察葛根芩连汤对大鼠血脂的影响,利用液质联用技术,对各组大鼠的粪便代谢组进行分析,寻找各组间共同的生物标记物,分析生物标记物的剂量依赖性。结果:高脂饲料饲养4 w后,高脂血症肥胖大鼠模型建立成功。给药7 w后,与正常对照组比较,模型对照组TC、TG、LDL-C含量明显升高(P<0.01或P<0.05),HDL-C含量明显降低(P<0.05),Lee′s指数显著升高(P<0.01)。与模型对照组比较,葛根芩连汤1.64、4.85、14.85 g/kg组TC、TG和HDL-C含量明显降低(P<0.05或P<0.01),葛根芩连汤4.85 g/kg组LDL-C含量明显降低(P<0.05),葛根芩连汤1.65 g/kg组FBG含量明显降低(P<0.05)。通过对各组大鼠粪便进行代谢组分析,成功鉴定了正离子模式中的5个物质:亚油酸、二十四碳六烯酸、切诺维乙醇酰胺、12-酮基去氧胆酸和3-氧代胆酸,负离子模式中未能鉴定到物质。除亚油酸和12-酮基去氧胆酸外,葛根芩连汤对生物标记物二十四碳六烯酸、切诺维乙醇酰胺和3-氧代胆酸的调节均具有较好的剂量依赖性。结论:葛根芩连汤能够有效改善高脂血症肥胖大鼠脂代谢异常,改善高脂血症肥胖大鼠脂代谢紊乱与调节不饱和脂肪酸的生物合成、胆汁酸代谢有关。Objective:To investigate the mechanism of Gegen Qinlian Decoction treating obesity by interfering with intestinal metabolism and lipid metabolism in rats.Methods:Rats were randomly divided into the control group and high fat group.Rats in high fat group were fed with high fat diet to establish hyperlipidemia obese rat model.After the model was established,rats in high fat group were randomly divided into the model group and Gegen Qinlian Decoction groups(14.85 g/kg,4.85 g/kg,1.65 g/kg),high fat diet and corresponding drugs were administered constantly for 7 weeks.The effects of Gegen Qinlian Decoction on blood lipids were observed.The fecal metabolites in each group were analyzed by LC-MS to search for common biomarkers between groups and analyze the dose dependence of biomarkers.Results:After 4 weeks of high fat feed,the hyperlipidemia obese rat model was successfully established.After 7 weeks of drug administration,compared with the control group,the contents of TC,TG and LDL-C in the model group were increased significantly(P<0.01,P<0.05),the content of HDL-C was decreased significantly(P<0.05),the Lee′s index was significantly increased(P<0.01).Compared with the model group,the contents of TC,TG and HDL-C in all doses of Gegen Qinlian Decoction groups were significantly decreased(P<0.05 or P<0.01),the content of LDL-C was significantly reduced in 4.85 g/kg Gegen Qinlian Decoction group(P<0.05).The content of FBG was significantly decreased in 1.65 g/kg Gegen Qinlian Decoction group(P<0.05).Five biomarkers in positive ion mode were successfully identified by metabolome analysis of feces in each group:linoleic acid,Tetracosahexaenoic acid,Cervonoyl ethanolamide,12-Ketodeoxycholic acid and 3-Oxocholic acid.In negative ion mode,no biomarker was observed.In addition to linoleic acid and 12-ketodeoxycholic acid,Gegen Qinlian Decoction showed regulative effect in good dose dependant manner on biomarkers hexacosahexaenoic acid,cenotivethanolamide and 3-oxocholic acid.Conclusion:Gegen Qinlian Decoction can effective

关 键 词：葛根芩连汤 高脂血症肥胖 粪便代谢组 肠道代谢 

分 类 号：R285.5[医药卫生—中药学]