基于肠道菌群和代谢组学探讨苦地丁减肥降脂作用机制  

Anti-obesity and lipid-lowering mechanism of Corydalis Bungeanae Herba: based on intestinal microflora and metabolomics

作　　者：付明海[1,2] 于红珍 包特日格乐 巴根那[1] FU Ming-hai;YU Hong-zhen;BAO Te-ri-ge-le;BA Gen-na(National Medical Products Administration Key Laboratory for Quality Control of Traditional Chinese Medicine(Mongolian Medicine),Inner Mongolia University for Nationalities,Tongliao 028000,China;School of Mongolian Medicine,Inner Mongolia University for Nationalities,Tongliao 028000,China)

机构地区：[1]内蒙古民族大学国家药监局中药(蒙药)质量控制重点实验室,内蒙古通辽028000 [2]内蒙古民族大学蒙医药学院,内蒙古通辽028000

出　　处：《中国中药杂志》2022年第11期3049-3058,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(81803845);内蒙古自治区蒙药食药源保护与利用创新团队建设项目(190301);内蒙古自治区蒙药工程技术研究中心开放基金项目(MDK2017072);蒙药研发国家地方联合工程研究中心开放基金课题(MDK2019044)。

摘　　要：通过肠道菌群和代谢组学分析探讨苦地丁Corydalis bungeana(CB)对肥胖大鼠的减肥降脂作用机制。高脂高糖(high-fat high-sugar diet, HFHS)饮食喂养大鼠10周建立肥胖模型,60只大鼠随机分为正常组、模型组、CB低剂量组(0.18 g·kg^(-1))、CB中剂量组(0.9 g·kg^(-1))、CB高剂量组(1.8 g·kg^(-1))和奥利司他组(0.03 g·kg^(-1))。每周观察记录大鼠体质量和食物摄入量;连续给药6周后处死大鼠取胃肠组织检测胃排空和小肠推进。ELISA法检测血清指标,取肝脏和肾周脂肪进行HE染色。收集大鼠粪便和血清进行16S rDNA测序和代谢组学检测,Spearman法分析差异菌群与差异代谢物之间相关性。结果显示,与肥胖模型鼠比较,CB组显著降低大鼠体质量、食物摄入量以及血清中的胆囊收缩素(CCK)、甘油三酯(TG)和总胆固醇(TC)水平,显著延缓胃排空,减少肝脏和肾周脂肪体积。模型组中Lachnospiraceae、Sutterellaceae显著下降,高剂量CB干预后有效上调了该菌落丰度;Prevotellaceae在HFHS诱导下显著上升,CB干预后可以明显下调其丰度。此外,glutaric acid、glyceric acid、hippuric acid、malic acid、glyceric acid、oxoglutaric acid、fumaric acid/succinic acid、oxoglutaric acid/isocitric acid、D-glucuronic acid、cholic acid为各组间主要差异代谢物,并与差异菌Sutterellaceae和Prevotellaceae呈高度相关性,参与调控三羧酸循环和葡萄糖、氨基酸、脂质代谢过程。该研究证明CB能有效改善体质量和血脂水平,减少脂肪体积,良性调控肠道菌群结构和血清代谢产物,达到减肥和降脂作用。This study aims to explore anti-obesity and lipid-lowering mechanism of Corydalis Bungeanae Herba(CB) based on intestinal microflora and metabolomics. Specifically, high-fat high-sugar diet(HFHS, 10 weeks) was used to induce obesity in rats. Then the model rats were randomized into the model group, low-dose(0.18 g·kg^(-1)), medium-dose(0.9 g·kg^(-1)), and high-dose(1.8 g·kg^(-1)) CBH groups, and orlistat group(0.03 g·kg^(-1)), 12 in each group. Rats which received normal diet were used as control. The body weight and feed intake of rats were recorded every week. After 6 weeks of administration, rats were killed and gastric emptying and small intestinal propulsion were examined. Enzyme-linked immunosorbent assay(ELISA) was employed to analyze serum indexes, and liver and perirenal fat were collected for haematoxilin-eosin(HE) staining. Rat feces and serum were gathered for 16 S rDNA sequencing and metabolomics analysis and Spearman′s correlation analysis was performed to explore the correlation between differential microflora and differential metabolites. The result showed that CBH extract decreased body weight, feed intake, and serum cholecystokinin(CCK), triglyceride(TG), and total cholesterol(TC), delayed gastric emptying, and reduced fat accumulation in liver and perirenal adiposity as compared with rats in the model group. In addition, Lachnospiraceae and Sutterellaceaecan significantly decreased in the model group, but CBH extract up-regulated their abundance. Moreover, the abundance of Prevotellaceae was significantly raised by HFHS, but CBH decreased it. Glutaric acid, glyceric acid, hippuric acid, malic acid, glyceric acid, oxoglutaric acid, fumaric acid/succinic acid, oxoglutaric acid/isocitric acid, D-glucuronic acid, cholic acid were the main deferentially expressed metabolites and significantly correlated with Sutterellaceae and Prevotellaceae. These key metabolites and microbiota mainly involved in tricarboxylic acid(TCA) cycle, glucose metabolism, amino acid metabolism, and energy metabolism.

关 键 词：苦地丁 肥胖 肠道菌群 代谢组学 

分 类 号：R285.5[医药卫生—中药学]