大柴胡汤通过CREB/PGC-1α通路保护营养型肥胖大鼠肝脏粒体功能  

Da Chaihutang Protects Liver Mitochondrial Function of Nutritionally Obese Rats via CREB/PGC-1α Pathway

作　　者：李龙春 李晓晔[2] 杜小华 柴铁劬 LI Long-chun;LI Xiao-ye;DU Xiao-hua;CHAI Tie-qu(Clinical Medical College of Acupuncture,Moxibustion and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Maternal and Child Health Hospital of Bao'an District,Shenzhen 518136,China;Graduate School of Guangxi University of Chinese Medicine,Nanning 530200,China)

机构地区：[1]广州中医药大学针灸康复临床医学院,广州510405 [2]深圳市宝安区妇幼保健院,广东深圳518136 [3]广西中医药大学研究生院,南宁530200

出　　处：《中国实验方剂学杂志》2021年第9期26-31,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广西自然科学基金面上项目(2018JJA140771)。

摘　　要：目的:观察大柴胡汤对营养型肥胖大鼠环磷腺苷效应元件结合蛋白(CREB)/过氧化物酶体增殖物激活受体γ共激活因子α(PGC-1α)通路的作用及肝脏线粒体的保护机制。方法:8周龄SD雄性大鼠120只,随机分为正常组20只和造模组100只。正常组给予大鼠维持饲料喂养,造模组给予高脂饲料喂养。造模成功大鼠随机分为模型组、阳性药(二甲双胍)组、大柴胡汤低、中、高剂量组(4.25,8.5,17 g·kg^(-1)),每组20只。电子天平称取并比较各组大鼠体质量,计算Lee’s指数,分光光度法检测肝脏线粒体膜电位,电镜检测线粒体超微结构,蛋白免疫印迹法检测PGC-1α蛋白表达和CREB磷酸化作用。结果:与正常组比较,模型组大鼠体质量及Lee’s指数显著增加(P<0.01),线粒体膜电位显著下降,PGC-1α蛋白表达和CREB磷酸化水平显著下降(P<0.01);与模型组比较,大柴胡汤能够明显降低肥胖大鼠体质量和Lee’s指数(P<0.05,P<0.01),提高肝脏线粒体膜电位(P<0.05,P<0.01)和保护线粒体结构完整性,上调PGC-1α蛋白表达和促进CREB磷酸化(P<0.05,P<0.01)。结论:大柴胡汤激活CREB/PGC-1α通路,保护线粒体结构与功能,有效抑制肥胖大鼠体质量增加。Objective: To observe the effects of Da Chaihutang on Cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB)/peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC-1α) pathway in nutritionally obese rats and the protective mechanism on liver mitochondria.Method: A total of 120 8-week-old male SD rats were randomly divided into a control group(n=20)and an experimental group(n=100). The rats in the control group were fed on a normal diet,while those in the experimental group were administered with a high-fat feed. Successfully modeled rats were randomly divided into a model group,a positive drug(metformin)group,and low-,medium-and high-dose Da Chaihutang groups(4.25, 8.5, and 17 g ? kg-1,respectively),with 20 rats in each group. After treatment with Da Chaihutang, the body weight, Lee’s index, liver mitochondrial membrane potential and mitochondrial ultrastructure,PGC-1α expression and CREB phosphorylation of each group were measured and compared.Result: Compared with the control group,the model group showed increased body weight and Lee’s index(P<0.01),whereas decreased mitochondrial membrane potential,PGC-1α expression,and CREB phosphorylation level(P<0.01). As compared with the model group,Da Chaihutang significantly reduced the body weight and Lee’s index of obese rats(P<0.05,P<0.01),enhanced liver mitochondrial membrane potential(P<0.05,P<0.01)to protect the integrity of mitochondrial structure,up-regulated PGC-1α expression and promoted CREB phosphorylation(P<0.05, P<0.01). Conclusion: Da Chaihutang protects the structure and function of mitochondria and inhibits weight gain in obese rats by activating the CREB/PGC-1α pathway.

关 键 词：大柴胡汤 营养性肥胖大鼠 线粒体 环磷腺苷效应元件结合蛋白(CREB)/过氧化物酶体增殖物激活受体γ共激活因子α(PGC-1α)通路 

分 类 号：R2-0[医药卫生—中医学] R22