天香丹联合Akk菌改善小鼠动脉粥样硬化的机制研究  

Study on mechanism of Tianxiangdan combined with Akkermansia muciniphila(Akk bacteria)to improve atherosclerosis(AS)in mice

作　　者：米洋 赵明芬[2] 倪昀 古丽葛娜·萨吾尔 凯迪努尔·买买提 MI Yang;ZHAO Mingfen;NI Yun;Guligona Sawuer;Kaydinur Maimaiti(The Fourth Clinical Medical College of Xinjiang Medical University,Urumqi 830054,China;Comprehensive Internal Medicine Department I,TCM Hospital Affiliated to XinJiang Medical University,Urumqi 830099,China)

机构地区：[1]新疆医科大学第四临床医学院,乌鲁木齐830054 [2]新疆医科大学附属中医医院综合内一科,乌鲁木齐830099

出　　处：《新疆医科大学学报》2025年第3期356-361,共6页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金项目(2021D01C227);新疆维吾尔自治区重大科技专项项目(2022A03019-1-3)。

摘　　要：目的探讨天香丹联合嗜黏蛋白阿克曼菌(Akkermansia muciniphila,Akk菌)改善小鼠动脉粥样硬化秽浊痰阻证的机制。方法选取30只雄性ApoE-/-小鼠为研究对象,6只作为空白组,予普通饲料室温饲养,其余24只予高脂饲料及气候箱连续干预8周,建立动脉粥样硬化(AS)秽浊痰阻证模型。造模成功后,将模型小鼠分为模型组[灌胃0.1 mL/10 g生理盐水]、Akk菌组[灌胃200μL聚丁二酸丁二醇醋(PBS,含5×10^(9)cfu Akk菌)]、天香丹组[灌胃天香丹(2.7g·kg^(-1)·d^(-1))]、Akk菌+天香丹组[灌胃天香丹(2.7 g·kg^(-1)·d^(-1))和200μL PBS(含5×10^(9)cfu Akk菌)],空白组[灌胃0.1 mL/10 g生理盐水],每天灌胃1次,连续4周。采用生化分析法检测血脂含量,通过酶标仪检测粪便胆汁酸,采用苏木精-伊红(HE)染色、油红O染色对比主动脉斑块病理学变化及脂质沉积,免疫印迹(WB)技术观测各组小鼠肝脏组织法尼醇X受体(farnesoid X receptor,FXR)、肝X受体(1iver X recepter,LXRa)、胆固醇7α-羟化酶(Cholesterol 7-alpha hydroxylase,CYP7A1)的蛋白水平表达。结果与模型组比较,Akk菌组、天香丹组、Akk菌+天香丹组甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平均显著降低(P<0.05),高密度脂蛋白(HDL-C)水平显著升高(P<0.05);血管病变减轻,主动脉管壁斑块减小,红染脂肪滴面积减少(P<0.05);粪便总胆汁酸(TBA)含量显著升高(P<0.05),肝脏FXR蛋白水平显著降低,LXRa、CYP7A1蛋白水平显著升高(P<0.05)。结论天香丹联合Akk菌可显著改善动脉粥样硬化秽浊痰阻证症状,其作用机制可能与降低FXR蛋白水平、升高LXRa、CYP7A1蛋白水平和改善脂质与胆汁酸代谢有关。Objective To explore the mechanism of Tianxiangdan combined with Akkermansia muciniphila(Akk bacteria)in improving atherosclerosis with turbid phlegm obstruction syndrome in mice.Methods 30 male ApoE-/-mice were selected as the research subjects,with 6 mice in the blank group and the rest 24 mice in the model group.The blank group was fed with normal diet and kept at room temperature,while the model group was fed with high-fat diet and continuously intervened in a climate chamber for 8 weeks to establish the atherosclerosis(AS)turbid phlegm obstruction syndrome model.After successful modeling,the model mice were divided into the model group[intragastric administration of 0.1 mL/10 g normal saline],Akk bacteria group[intragastric administration of 200μL PBS(containing 5×10^(9)cfu Akk bacteria)],Tianxiangdan group[intragastric administration of Tianxiangdan(2.7 g·kg^(-1)·d^(-1))],Akk bacteria+Tianxiangdan group[intragastric administration of Tianxiangdan(2.7 g·kg^(-1)·d^(-1))and 200μL PBS(containing 5×10^(9)cfu Akk bacteria)]and the blank group[intragastric administration of 0.1 mL/10 g normal saline].Each group was intragastrically administered once a day for 4 consecutive weeks.Biochemical analysis was used to detect lipid content;the total bile acid(TBA)in feces was detected by an enzyme-linked immunosorbent assay(ELISA);HE staining and Oil Red O staining were used to compare the pathological changes and lipid deposition of aortic plaques;Western blotting(WB)was used to observe the protein expression levels of farnesoid X receptor(FXR),liver X receptor(LXRa)and cholesterol 7α-hydroxylase(CYP7A1)in liver tissues of each group.Results Compared with model group,the levels of triglycerides(TG),total cholesterol(TC)and low-density lipoprotein(LDL-C)in the Akk bacteria group,Tianxiangdan group,and Akk bacteria+Tianxiangdan group were significantly decreased(P<0.05),and the level of high-density lipoprotein(HDL-C)was significantly increased(P<0.05);the vascular disease wasdecreased,the aortic wall plaque was d

关 键 词：天香丹 嗜黏蛋白阿克曼菌 胆汁酸代谢 动脉粥样硬化 秽浊痰阻证 

分 类 号：R256[医药卫生—中医内科学]