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黄连解毒汤调控肠道菌群抗apoE^(-/-)小鼠非酒精性脂肪性肝病和动脉粥样硬化的研究 被引量:10

Study on Huanglian Jiedu Decoction Regulating Intestinal Flora Against Non-alcoholic Fatty Liver Disease and Atherosclerosis in apoE^(-/-)mice
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摘要 目的:观察黄连解毒汤对高脂饮食导致的apoE基因敲除(apoE^(-/-))小鼠血脂水平、肠道菌群、单胺氧化酶(monoamine oxidase,MAO)活力及其脂肪肝和血管动脉粥样硬化(atherosclerosis,AS)斑块形成的影响。方法:8周龄雌性apoE^(-/-)小鼠给予高脂饮食,治疗组同时给予黄连解毒汤或阿托伐他汀干预,4周后常规检测血脂水平,检测血浆和肝脏的MAO活力;取小鼠结肠内容物,16S rRNA相对应的DNA序列(16S rDNA)检测肠道菌群,干预18周后病理检测主动脉血管动脉粥样硬化(AS)斑块和脂肪肝形成情况。结果:高脂饮食导致apoE^(-/-)小鼠血浆总胆固醇(cholesterol,TC)和低密度脂蛋白(low density lipoprotein,LDL)水平升高(P<0.001),差异有统计学意义;血浆和肝脏检测MAO活性增高(P<0.05),差异有统计学意义;结肠菌群α多样性增加,变形菌门增加,拟杆菌门减少。黄连解毒汤干预4周,血脂水平无明显改变,血浆和肝脏MAO活力降低(P<0.05),差异有统计学意义;结肠菌群α多样性降低,厚壁菌门和变形菌门减少,拟杆菌门和疣微球菌门增加;干预18周高脂导致apoE^(-/-)小鼠肝脏脂肪肝病变和主动脉血管AS斑块形成,黄连解毒汤明显干预改善脂肪肝和主动脉血管AS斑块病变程度。结论:黄连解毒汤可能通过调节肠道菌群失衡,降低MAO活性,从而抑制高脂饮食导致apoE^(-/-)小鼠非酒精性脂肪性肝病(non-alcholic fatty liver disease,NAFLD)和AS斑块的形成。 Objective:To observe the effect of Huanglian Jiedu Decoction on plasma lipid level,intestinal flora,monoamine oxidase activity,hepatic adipogenesis and atherosclerotic plaque formation in apoE gene knockout(apoE^(-/-))mice induced by Western diet.Methods:In the present study,8 week-old homozygous female apoE^(-/-)mice were fed with a normal chow diet(CD),a high cholesterol Western diet(WD)and WD supplemented with Huanglian Jiedu Decoction(HLJDD)/atorvastatin(Atr).After 4 weeks,the levels of blood lipid in plasma,and activity of monoamine oxidase in plasma and liver were measured.Intestinal flora in colon was detected by 16 Sr DNA sequence.After 18 weeks of intervention,the pathological changes of liver and aorta were detected by oil-red O staining.Results:For 8 week-old apoE^(-/-)mice with WD for another 4 weeks,WD increased plasma TC and LDL levels in apoE^(-/-)mice(P<0.001).WD increased the activity of monoamine oxidase(MAO)in plasma and liver(P<0.05).WD also induced the imbalance of intestinal flora,increasedαdiversity of colonic flora,increased the abundance of Proteobacteria,and decreased Bacteroidetes.HLJDD had no significant change in plasma lipid level,but decreased MAO activity in plasma and liver(P<0.05),and reducedαdiversity of colonic flora,decreased the abundance of Firmicutes and Proteobacteria,and increased Bacteroidetes and Verrucomicrobia in colon of apoE^(-/-)mice.After 18 weeks of intervention,WD increased the number and area of aortic plaques in apoE^(-/-)mice;liver oil red O staining was positive;HLJDD reduced degree of aortic AS plaques,and weakened liver oil-red O staining.Conclusion:HLJDD may regulate the imbalance of intestinal microorganisms,decrease the activity of monoamine oxidase,and inhibit non-alcoholic fatty liver disease(NAFLD)and atherosclerosis(AS)plaques in apoE^(-/-)mice induced by WD.
作者 姜楠 薛欣 张媛媛 陈晨 曾辉 马雅銮 JIANG Nan;XUE Xin;ZHANG Yuan-yuan;CHEN Chen;ZENG Hui;MA Ya-luan(Institute of Basic Theory,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Beijing Key Laboratory of Emerging Infectious Diseases,Beijing 100015,China)
出处 《中国中医基础医学杂志》 CAS CSCD 北大核心 2021年第6期927-931,994,共6页 JOURNAL OF BASIC CHINESE MEDICINE
基金 中国中医科学院中医基础理论研究所基本科研业务费自主选题项目(YZ-1702)-基于黄连解毒汤调控肠道菌群失衡的抗动脉粥样硬化的机制研究。
关键词 黄连解毒汤 肠道菌群 单胺氧化酶 非酒精性脂肪性肝病 动脉粥样硬化 Huanglian Jiedu Decoction Intestinal flora Monoamine oxidase Non-alcoholic fatty liver disease Atherosclerosis
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