益糖康调控PGC1α-NRF1/2-TFAM通路对db/db小鼠棕色脂肪的影响  

Effects of Yitangkang on Brown Fat in db/db Mice by Regulating PGC1α-NRF1/2-TFAM Pathway

作　　者：张晖[1] 孙立亚 王庆峰 孙贵炎 申鑫惠 胡锦浩 石岩[1] 杨宇峰[1] ZHANG Hui;SUN Liya;WANG Qingfeng;SUN Guiyan;SHEN Xinhui;HU Jinhao;SHI Yan;YANG Yufeng(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《中国中医药信息杂志》2025年第4期79-84,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家中医药管理局青年岐黄学者项目(2022年);辽宁省应用基础研究计划(2023JH2/101300050);辽宁省中央引导地方科技发展专项(2019JH6/10200009);辽宁省“兴辽英才计划”青年拔尖人才项目(XLYC1807145)。

摘　　要：目的观察益糖康对db/db小鼠棕色脂肪产热及线粒体生物发生PGC1α-NRF1/2-TFAM通路的影响,探讨其调节糖脂代谢机制。方法27只6周龄db/db小鼠随机分为模型组、益糖康组(30 g/kg)和利拉鲁肽组(200μg/kg),另将9只同周龄db/m小鼠作为正常组,分别予药物或生理盐水干预6周。每周定时测量小鼠体质量及空腹血糖(FBG),干预结束后禁食不禁水进行口服葡萄糖耐量试验,生化分析仪测定小鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,HE染色观察肩胛区棕色脂肪组织(BAT)形态,RT-qPCR和Western blot检测肩胛区BAT产热相关因子[解偶联蛋白1(UCP1)、PR结构域蛋白16(PRDM16)、过氧化物酶体增殖物激活受体γ共激活因子-1α(PCG-1α)]和线粒体生物发生相关因子[核呼吸因子(NRF)1、NRF2、线粒体转录因子A(TFAM)]mRNA及蛋白表达。结果与正常组比较,模型组小鼠体质量、FBG、糖耐量曲线下面积(AUC)及血清TC、TG、LDL-C含量明显升高(P<0.01),HDL-C含量明显降低(P<0.01);肩胛区BAT细胞变大,出现白色空泡,脂滴增多,UCP1、PRDM16、PGC-1α、NRF1、NRF2、TFAM mRNA和蛋白表达降低(P<0.01)。与模型组比较,益糖康组及利拉鲁肽组小鼠体质量、FBG、糖耐量AUC及血清TC、TG、LDL-C含量明显降低(P<0.01),HDL-C含量明显升高(P<0.01);BAT细胞直径减小、排列紧密、形状规则,细胞间毛细血管丰富,UCP1、PRDM16、PGC-1α、NRF1、NRF2、TFAM mRNA和蛋白表达升高(P<0.01)。结论益糖康可通过PGC1α-NRF1/2-TFAM通路调控db/db小鼠线粒体生物发生,激活棕色脂肪,发挥改善db/db小鼠糖脂代谢紊乱作用。Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1αrelated to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

关 键 词：益糖康 2型糖尿病 棕色脂肪 线粒体生物发生 PGC1α-NRF1/2-TFAM通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]