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基于代谢组学探究疏调气机汤治疗甲状腺功能减退症的作用机制

Investigation of the mechanism of action of Shutiao Qiji Decoction in the treatment of hypothyroidism based on metabolonics
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摘要 目的采用非靶向代谢组学方法分析甲状腺功能减退症大鼠血清标志物,探究疏调气机汤对甲状腺功能减退症的治疗作用机制。方法对适应性喂养1周后大鼠进行随机分组,分为造模组和正常组,造模组大鼠持续10 d丙硫氧嘧啶灌胃给药造模,正常组灌胃同等体积饮用水。造模结束后检测血清指标是否符合临床疾病诊断标准,并结合造模期间大鼠状态,判定造模成功。将造模成功大鼠进行分组,分为模型对照组、阳性药(优甲乐)组、疏调气机汤低浓度组、疏调气机汤中浓度组、疏调气机汤高浓度组,分别给药6周,正常组、模型对照组以同等体积饮用水灌胃。6周后大鼠腹主动脉取血,离心取上清,ELISA试剂盒检测及非靶向代谢组学检测。结果疏调气机汤可明显降低甲减大鼠促甲状腺激素(TSH)水平,可明显升高游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)表达水平(P<0.05)。代谢组学分析血清标记物,正常组与模型对照组比较,共有312个显著差异代谢物,其中111个代谢物水平上调,198个代谢物水平下调;疏调气机汤高剂量组与模型对照组比较,共有91个显著差异代谢物,其中有47个代谢物水平上调,39个代谢物水平下调,代谢物多以生物碱类、缩氨酸类、聚酮类为主。KEGG分析代谢路径主要与心碳循环、氨基酸生物合成、胆汁分泌相关。结论疏调气机汤对甲状腺功能减退症大鼠具有良好的治疗作用,为疏调气机汤治疗甲减的临床用药与治疗提供实验依据,为甲减的中医疗法提供新思路。 Objective To investigate the mechanism of therapeutic effect of Shutiao Qiji Decoction on hypothyroidism by analyzing serum markers in hypothyroidism rats using non-targeted metabolomics method.Methods The rats were randomly grouped into modeling and normal groups after one week of adaptive feeding,and the modeling rats were administered propylthiouracil by gavage for 10 days to model,while the normal group was given the same volume of drinking water by gavage.At the end of the modeling period,the rats were tested to determine whether the serum indexes met the diagnostic criteria of clinical diseases and the status of the rats during the modeling period to determine the success of the modeling.The rats were grouped into model group,positive drug(eugenol)group,Shutiao Qiji Decoction low concentration group,Shutiao Qiji Decoction medium concentration group and Shutiao Qiji Decoction high concentration group,and administered with the same volume of drinking water for 6 weeks in the normal group and model group.6 weeks later,blood was collected from the abdominal aorta of the rats,and the supernatant was centrifuged for ELISA kit detection and non-targeted metabolomics detection.Results Shutiao Qiji Decoction could significantly reduce TSH levels and significantly increase FT3 and FT4 expression levels in hypothyroid rats(P<0.05).When comparing the normal group with the model group,there were 312 significantly different metabolites,of which 111 metabolites were up-regulated and 198 metabolites were down-regulated;When comparing the high dose group with the model group,there were 91 significantly different metabolites,of which 47 metabolites were up-regulated and 39 metabolites were down-regulated,mostly alkaloids,condensates and polyketides.The metabolic pathways analyzed by KEGG were mainly related to carbon cycle,amino acid biosynthesis and bile secretion.Conclusion The therapeutic effect of Shutiao Qiji Decoction on hypothyroidism rats is good,which provides an experimental basis for the clinical use and treatment of hypothyroidism with Shutiao Qiji Decoction and a new idea for the Chinese medicine of hypothyroidism.
作者 郭爽 张利军 龙小妹 古建兴 刘海鹏 范源 GUO Shuang;ZHANG Lijun;LONG Xiaomei;GU Jianxing;LIU Haipeng;FAN Yuan(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;The Second Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming 650041,China;The First Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming 650021,China)
出处 《药学研究》 CAS 2024年第3期209-213,226,共6页 Journal of Pharmaceutical Research
基金 云南省高校中西医结合防治甲状腺病重点实验室(No.20190925) 云南省科技厅科技计划项目-应用基础研究计划(No.202101AZ010001-015) 云南省“万人计划”名医专项(No.YNWR-MY-2020-084) 云南省科技人才与平台计划(No.202105AE160018) 云南中医药大学第二附属医院中医特色专科(内分泌科)建设项目。
关键词 疏调气机汤 甲状腺功能减退症 代谢组学 名老中医经验 Shutiao Qiji Decoction Hypothyroidism Metabolomics Experience of famous veteran Chinese medicine practitioners
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