肥胖痰湿证模型大鼠脂肪组织代谢相关基因启动子甲基化状态及温胆汤的干预作用  

Methylated Status of Adipose Tissue Metabolism-related Gene Promoters in Obesity of Phlegm-dampness Syndrome Model Rats and Intervention Effect of Wendan Decoction (温胆汤)

作　　者：杨海燕[1] 程绍民[1] 喻松仁[1] 夏循礼[1] 王萍[1] YANG Haiyan;CHENG Shaomin;YU Songren;XIA Xunli;WANG Ping(School of Traditional Chinese Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang,330000)

机构地区：[1]江西中医药大学中医学院,江西省南昌市330000

出　　处：《中医杂志》2020年第8期706-710,共5页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81302907);江西中医药大学校级重点学科(11413015)。

摘　　要：目的探讨肥胖痰湿证模型大鼠脂肪组织代谢相关基因启动子甲基化的改变以及温胆汤干预的可能机制。方法采用喂饲高脂饲料8周建立肥胖痰湿证大鼠模型,将造模成功大鼠采用随机数字法分为温胆汤组和模型组各10只,另设正常组大鼠10只。造模后各组大鼠均采用普通饲料喂养,同时温胆汤组给予温胆汤15g/(kg·d)灌胃,模型组和正常组给予同体积蒸馏水灌胃,共干预4周。采用甲基化DNA免疫共沉淀测序(MeDIP-seq)方法对各组大鼠腹腔脂肪组织启动子甲基化差异基因与代谢相关基因进行筛选,并用焦磷酸测序验证基因启动子甲基化检测结果。结果肥胖痰湿证与代谢相关的基因分别有19个启动子甲基化程度降低、36个启动子甲基化程度增加。温胆汤干预肥胖痰湿证后,与代谢相关的甲基化差异基因有14个甲基化程度降低,38个甲基化程度增加,且其中与肥胖痰湿证有关的启动子甲基化差异基有7条,即B4galt7、Elof1、Iws1、Kynu、Sc5d、Mutyh、Tgif2。结论肥胖痰湿证模型大鼠存在着脂肪组织代谢相关基因启动子甲基化状态的改变,温胆汤对代谢相关基因启动子的甲基化具有一定的调控作用。Objective To explore methylated changes of adipose tissue metabolism-related gene promoters in obesity of phlegm-dampness syndrome model rats and the possible intervention mechanism of Wendan Decoction(温胆汤). Methods Rat models of obesity of phlegm-dampness syndrome were established by feeding a high-fat diet for 8 weeks, and the successful modeling rats were divided into Wendan Decoction group and model group according to random number table method, with 10 rats in each group. Another 10 rats were set as normal group. After the modeling, rats in all groups were fed with common feed. At the same time, the Wendan Decoction group was given 15 g/(kg·d) Wendan Decoction by gavage, and the model group and normal group were given the same volume of distilled water, treating for 4 weeks. Methylated DNA immunoprecipitation sequencing(MeDIP-seq) method was used to screen promoter methylation differential genes and metabolism-related genes in rat abdominal adipose tissue of each group, and the results of promoter methylation detection were verified by pyrosequencing. Results In the metabolism-related genes in obesity of phlegm-dampness syndrome, methylation degrees of 19 promoters were decreased and the methylation degrees of 36 promoters were increased. After the intervention of Wendan Decoction in obesity of phlegm-dampness syndrome, the methylation degrees of 14 methylated differential genes related to metabolism were decreased, and the methylation degrees of 38 methylated differential genes were increased, in which there were 7 differential genes of promoter methylation related to obesity of phlegm-dampness syndrome, namely B4 galt7, Elof1, Iws1, Kynu, Sc5 d, Mutyh and Tgif2. Conclusion There are changes in the methylated status of adipose tissue metabolism-related gene promoters in obesity of phlegm-dampness syndrome model rats, and Wendan Decoction has a certain regulatory effect on the methylation of metabolism-related gene promoters.

关 键 词：肥胖 痰湿证 温胆汤 脂肪组织 代谢 启动子甲基化 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]