刺五加乙酸乙酯部位对ApoE^(-/-)动脉粥样硬化小鼠肠道菌群的影响  

Effect of Ethyl Acetate Extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on Intestinal Flora in ApoE^(-/-) Mice with Atherosclerosis

作　　者：贾艾玲 张宇航[2] 刁元元 石羽文 姜孟成 李军鸽 邱野 邱智东[2] 傅超美[1] JIA Ai-ling;ZHANG Yu-hang;DIAO Yuan-yuan;SHI Yu-wen;JIANG Meng-cheng;LI Jun-ge;QIU Ye;QIU Zhi-dong;FU Chao-mei(School of Pharmacy,Chengdu University of Traditional Chinese Medicine(TCM),Chengdu 611137,China;School of Pharmaceutical Sciences,Key Laboratory of TCM Active Ingredient,Ministry of Education,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]成都中医药大学药学院,成都611137 [2]长春中医药大学药学院,中药有效成分省部共建教育部重点实验室,长春130117

出　　处：《中国实验方剂学杂志》2022年第5期108-115,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：吉林省科技厅项目(20200602034ZP);长春中医药大学杏林学者工程青年科学家项目(QNKXJ2-2021ZR26)。

摘　　要：目的:观察刺五加乙酸乙酯部位对高脂饮食诱导的载脂蛋白E基因敲除(ApoE^(-/-))小鼠的影响,探讨其通过调控肠道菌群从而治疗动脉粥样硬化的作用机制。方法:32只8周龄雄性;小鼠随机分为模型组,瑞舒伐他汀组(10 mg·kg^(-1))和刺五加乙酸乙酯部位高、低剂量组(75,25 mg·kg^(-1)),每组8只。8只C57BL/6小鼠作为空白组。连续给药8周后,取血测定其血脂水平;采用酶联免疫吸附测定法(ELISA)试剂盒检测小鼠血清中相关指标含量;苏木素-伊红(HE)染色法观察小鼠主动脉病理形态;收集盲肠内容物采用16S rRNA扩增子测序检测肠道菌群。结果:与空白组比较,模型组小鼠斑块面积显著增加并伴有炎性浸润,升高甘油三酯(TG),总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)含量,增加炎症因子和血管内皮因子诱导型一氧化氮合成酶(iNOS)含量,降低高密度脂蛋白胆固醇(HDL-C)含量;与模型组比较,瑞舒伐他汀组和刺五加乙酸乙酯部位高、低剂量组能改善小鼠主动脉斑块沉积,降低TG,TC,LDL-C,炎症因子和iNOS含量,升高HDL-C含量。与空白组比较,模型组厚壁菌门和变形菌门相对丰度升高,拟杆菌门相对丰度降低。Alpha和Beta多样性分析显示,各组样本能够显著分离,模型组肠道菌群物种总数和丰度较低;与模型组相比,刺五加乙酸乙酯部位可提高有益菌的相对丰度,降低致病菌的相对丰度。结论:刺五加乙酸乙酯部位主要为黄酮类成分,能够通过调控肠道菌群来治疗动脉粥样硬化,改善高脂饮食喂养ApoE;小鼠主动脉病理变化,作用机制可能与其能够降低炎症因子水平、提高抗氧化能力、修复肠道菌群结构紊乱现象有关。Objective:To observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout(ApoE^(-/-))mice,and explore its mechanism of treating atherosclerosis by regulating intestinal flora. Method: Thirty-two 8-week-old male ApoE;mice were randomly divided into model group,rosuvastatin group(10 mg·kg^(-1)),high-,low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis(75,25 mg·kg^(-1)),with8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration, blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin(HE)staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16 S rRNA amplicon sequencing was used to detect intestinal flora. Result: Compared with the blank group,the plaque area of the model group was significantly increased with inflammatory infiltration,the contents of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),inflammatory factors and inducible nitric oxide synthase(iNOS)were increased,while the content of high-density lipoprotein cholesterol(HDL-C)was decreased. Compared with the model group,rosuvastatin group and high-and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque,reduce the contents of TG,TC,LDL-C,inflammatory factors and iNOS,and increase the content of HDL-C. Compared with the blank group,the relative abundances of Firmicutes and Proteobacteria in the model group increased,while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated,and the total number and abundance of intestinal flora species in the model group were low. Compared with

关 键 词：刺五加 乙酸乙酯部位 肠道菌群 载脂蛋白E基因敲除(ApoE^(-/-))小鼠 动脉粥样硬化 炎症因子 抗氧化活性 血管内皮因子 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学]