半夏白术天麻汤下调ApoE^(-/-)小鼠TMAO代谢的作用研究  

Effect of Banxia Baizhu Tianma Decoction on Down-regulating TMAO Metabolism in ApoE^(-/-)Mice

作　　者：李继军[1] 荣雅琪 孟宪卿[2] 姜月华[2] LI Jijun;RONG Yaqi;MENG Xianqing;JIANG Yuehua(Jinan Hospital of Traditional Chinese Medicine,Jinan 250012,Shandong,China)

机构地区：[1]济南市中医医院,济南250012 [2]山东中医药大学附属医院,济南250012

出　　处：《中西医结合心脑血管病杂志》2023年第18期3336-3341,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金面上项目(No.82174177);山东省医药卫生科技发展计划项目(No.2017WSJ34)。

摘　　要：目的:通过靶向超高效液相色谱-电喷雾串联质谱法(UPLC-ESI-MS/MS)检测半夏白术天麻汤对载脂蛋白E基因敲除(ApoE^(-/-))小鼠血浆氧化三甲胺(TMAO)相关代谢物及TMAO代谢途径的影响,探讨半夏白术天麻汤改善动脉硬化的药理作用机制。方法:选取雄性ApoE^(-/-)小鼠36只,高脂高胆固醇饮食12周后,随机分为半夏白术天麻汤组[17.8 g/(kg·d)]、瑞舒伐他汀钙组[0.08 mg/(kg·d)]和ApoE^(-/-)模型组,灌胃8周,以C57BL/6J小鼠作为C57正常对照组(12只)。UPLC-ESI-MS/MS定量检测小鼠血浆TMAO及相关代谢物水平,苏木精-伊红(HE)染色观察主动脉形态,免疫组化观察CD 36、NOD样受体热蛋白结构域相关蛋白3(NLRP3)的分布,酶联免疫吸附法(ELISA)测定血浆白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)含量。结果:半夏白术天麻汤可降低ApoE^(-/-)小鼠血浆左旋肉碱、甜菜碱、肌酐、三甲胺、TMAO水平(P<0.05或P<0.01),改善血管形态、减少脂质空泡和胶原沉积在血管组织中,并减少CD 36、NLRP3在主动脉的分布(P<0.01),降低血浆IL-1β、IL-18含量(P<0.01)。结论:半夏白术天麻汤可减轻ApoE^(-/-)小鼠动脉粥样硬化,其作用与降低血浆TMAO相关代谢物及TMAO代谢途径相关。Objective:To detect the effect of Banxia Baizhu Tianma Decoction(BBTD)on Trimethylamine N-oxide(TMAO)related metabolites and TMAO metabolic pathway in ApoE^(-/-)mice.Methods:A total of 36 male ApoE^(-/-)mice were fed with a high-fat and high-cholesterol diet for 12 weeks,then randomly divided into three groups:BBTD group 17.8 g/(kg·d),rosuvastatin group 0.08 mg/(kg·d),and model group,administered orally for 8 weeks;C57BL/6J mice were used as the standard control group(n=12).UPLC-ESI-MS/MS was used to detect the levels of TMAO and related metabolites in ApoE^(-/-)mice;hematoxylin-eosin(HE)staining was used to observe aorta morphology,the distribution of CD 36,and NLRP3 was observed by immunohistochemistry;enzyme-linked immunosorbent assay(ELISA)was used to measure the contents of plasma interleukin-1β(IL-1β)and interleukin-18(IL-18).Results:BBTD could significantly reduce the plasma levels of L-carnitine,betaine,creatinine,TMA,and TMAO in ApoE^(-/-)mice,improve the aortic morphology,decrease the density of CD 36 and NLRP3 in aorta and decrease plasma IL-1βand IL-18 levels(P<0.01).Conclusion:BBTD could effectively alleviated atherosclerosis in ApoE^(-/-)mice,and the efficiency is related to the decrease of TMAO-related metabolites and TMAO metabolic pathway.

关 键 词：动脉粥样硬化 半夏白术天麻汤 氧化三甲胺 载脂蛋白E基因敲除 实验研究 

分 类 号：R285.5[医药卫生—中药学]