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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
Received:02 November 2021,
Published Online:27 December 2021,
Published:05 March 2022
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贾艾玲,张宇航,刁元元等.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[J].中国实验方剂学杂志,2022,28(05):108-115.
JIA Ai-ling,ZHANG Yu-hang,DIAO Yuan-yuan,et al.Effect of Ethyl Acetate Extract ofAcanthopanacis Senticosi Radix et Rhizoma seu Caulis on Intestinal Flora in ApoE-/- Mice with Atherosclerosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):108-115.
贾艾玲,张宇航,刁元元等.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[J].中国实验方剂学杂志,2022,28(05):108-115. DOI: 10.13422/j.cnki.syfjx.20220152.
JIA Ai-ling,ZHANG Yu-hang,DIAO Yuan-yuan,et al.Effect of Ethyl Acetate Extract ofAcanthopanacis Senticosi Radix et Rhizoma seu Caulis on Intestinal Flora in ApoE-/- Mice with Atherosclerosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):108-115. DOI: 10.13422/j.cnki.syfjx.20220152.
目的
2
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
2
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
2
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
2
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
2
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
2
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
), with 8 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 16S rRNA amplicon sequencing was used to detect intestinal flora.
Result
2
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 the model group, ethyl acetate extract of
Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria.
Conclusion
2
Ethyl acetate extract of
Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids, which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE
-/-
mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors, improve antioxidant capacity and repair the disorder of intestinal flora structure.
李英 , 龚宝莹 , 朱建华 , 等 . 国医大师朱良春从痰瘀论治颈动脉不稳定斑块的学术经验 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 23 ): 195 - 200 .
胡娟 , 汪星辉 , 高杉 , 等 . 肠道菌群在心血管疾病中的作用及其机制研究进展 [J]. 中国药理学通报 , 2019 , 35 ( 11 ): 1496 - 1500 .
HUANG H M , JIANG X , HAO M L , et al . Identification of biomarkers in macrophages of atherosclerosis by microarray analysis [J]. Lipids Health Dis , 2019 , 18 ( 1 ): 107 .
HWANG E , KIM G W , SONG K D , et al . The enhancing effect of Acanthopanax sessiliflorus fruit extract on the antibacterial activity of porcine alveolar 3D4/31 macrophages via NF- κ B 1 and lipid metabolism regulation [J]. Asian Austral J Anim , 2019 , 32 ( 11 ): 1776 - 1788 .
SUMIYOSHI M , KIMURA Y . Effects of Eleutherococcus senticosus cortex on recovery from the forced swimming test and fatty acid beta-oxidation in the liver and skeletal muscle of mice [J]. Nat Prod J , 2016 , 6 ( 1 ): 49 - 55 .
NISHIDA M , KONDO M , SHIMIZU T , et al . Antihyperlipidemic effect of Acanthopanax senticosus (Rupr. et Maxim) Harms leaves in high-fat-diet fed mice [J]. J Sci Food Agr , 2016 , 96 ( 11 ): 3717 - 3722 .
WANF Y H , MENG Y , ZHAI C , et al . The chemical characterization of Eleutherococcus senticosus and Ci-wu-jia tea using UHPLC-UV-QTOF/MS [J]. Int J Mol Sci , 2019 , 20 ( 3 ): 475 .
ATRAHIMOVICH D , AVNI D , KHATIB S . Flavonoids-macromolecules interactions in human diseases with focus on Alzheimer,atherosclerosis and cancer [J]. Antioxidants (Basel) , 2021 , 10 ( 3 ): 423 .
SCHIRMEI M , SMEEKENS S P , VILAMAKIS H , et al . Linking the human gut microbiome to inflammatory cytokine production capacity [J]. Cell , 2016 , 167 ( 4 ): 1125 - 1136 .
GENA-ZATORSKY N , SEFIK E , KUA L , et al . Mining the human gut microbiota for immunomodulatory organisms [J]. Cell , 2017 , 168 ( 5 ): 928 - 943 .
KHOSRAVI A , YÁÑEZ A , PRICE J G , et al . Gut microbiota promote hematopoiesis to control bacterial infection [J]. Cell Host Microbe , 2014 , 15 ( 3 ): 374 - 381 .
PLUMP A S , SMITH J D , HAYEK T , et al . Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells [J]. Cell , 1992 , 71 ( 2 ): 343 - 353 .
国家药典委员会 . 中华人民共和国药典:一部 [M]. 北京 : 中国医药科技出版社 , 2020 : 425 - 426 .
WANG Z , KLIPFELL E , BENNETT B J , et al . Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease [J]. Nature , 2011 , 472 ( 7341 ): 57 - 63 .
易琼 , 李雅 , 郭志华 , 等 . 基于“心受气于脾”探讨心痛泰调控p38 MAPK/AP-1对动脉粥样硬化兔的中医证候和VSMC胶原纤维的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 19 ): 56 - 65 .
何祥 , 李国莺 , 汪丹丹 , 等 . 基于NLRP3炎症小体探讨地奥心血康抗动脉粥样硬化作用机制 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 20 ): 55 - 62 .
罗欢 , 何兰 , 何迎春 , 等 . 核因子- κ B (NF- κ B)与核因子E 2 相关因子2(Nrf2)信号通路交互对结直肠癌防治及中药研究的启示 [J]. 中国临床药理学杂志 , 2021 , 37 ( 10 ): 1266 - 1271,1276 .
LIU J F , ZHANG T H , WANG Y Y , et al . Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota [J]. Aging (Albany NY) , 2020 , 12 ( 4 ): 3791 - 3806 .
王明亮 , 丁永芳 , 印鑫 , 等 . 基于肠-肝-肾轴的肝纤维化与肾纤维化研究进展 [J]. 药学学报 , 2021 , 56 ( 1 ): 9 - 20 .
JIN M , QIAN Z , YIN J , et al . The role of intestinal microbiota in cardiovascular disease [J]. J Cell Mol Med , 2019 , 23 ( 4 ): 2343 - 2350 .
张留代 , 熊伟 , 许青 , 等 . 基于“心与小肠相表里”探讨松萝抗大鼠动脉粥样硬化及对回肠菌群的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 14 ): 36 - 46 .
TROMPETTE A , GOLLWITZER E S , PATTARONI C , et al . Dietary fiber confers protection against flu by shaping Ly6c - patrolling monocyte hematopoiesis and CD8 + T cell metabolism [J]. Immunity , 2018 , 48 ( 5 ): 992 - 1005 .
ULLERYD M A , PRAHL U , BÖRSBO J , et al . The association between autonomic dysfunction, inflammation and atherosclerosis in men under investigation for carotid plaques [J]. PLoS One , 2017 , 12 ( 4 ): e0174974 .
BRANDSMA E , KLOOSTERHUIS N J , KOSTER M , et al . A proinflammatory gut microbiota increases systemic inflammation and accelerates atherosclerosis [J]. Circ Res , 2019 , 124 ( 1 ): 94 - 100 .
TILG H , ZMORA N , ADOLPH T E , et al . The intestinal microbiota fuelling metabolic inflammation [J]. Nat Rev Immunol , 2020 , 20 ( 1 ): 40 - 54 .
HU X R , MA R S , CAO J L , et al . PTPN2 negatively regulates macrophage inflammation in atherosclerosis [J]. Aging (Albany NY) , 2020 , 13 ( 2 ): 2768 - 2779 .
DOUGLAS G , HALE A B , PATEL J , et al . Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression [J]. Cardiovasc Res , 2018 , 114 ( 10 ): 1385 - 1399 .
MIYOSHI T , LI Y , SHIH D M , et al . Deficiency of inducible NO synthase reduces advanced but not early atherosclerosis in apolipoprotein E-deficient mice [J]. Life Sci , 2006 , 79 ( 6 ): 525 - 531 .
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