牛蒡子苷对胰岛素抵抗型小鼠糖脂代谢调节及心肌保护的作用  

Arctiin improves glucolipid metabolism and protects myocardial tissuein insulin-resistant mice

作　　者：朱心瑶 刘治国 杨雪 魏叶[3] 阚荣生 王志荣 ZHU Xinyao;LIU Zhiguo;YANG Xue;WEI Ye;KAN Rongsheng;WANG Zhirong(School of First Clinical Medicine,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;Suqian First Hospital,Suqian,Jiangsu 223899;Department of Cardiology,Fenjinting Hospital ofSihong County,Suqian,Jiangsu 223900;Department of Cardiology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221002)

机构地区：[1]徐州医科大学第一临床医学院,江苏徐州221004 [2]宿迁市第一人民医院,江苏宿迁223899 [3]泗洪县分金亭医院心内科,江苏宿迁223900 [4]徐州医科大学附属医院心内科,江苏徐州221002

出　　处：《徐州医科大学学报》2021年第2期102-106,共5页Journal of Xuzhou Medical University

基　　金：江苏省青年医学人才基金资助项目(QNRC2016480)。

摘　　要：目的研究牛蒡子苷(ARC)对胰岛素抵抗型(IR)小鼠的糖脂代谢调节及对心肌纤维化的作用。方法选取C57BL/6J雄性小鼠高脂饲料饲养,构建IR小鼠模型。将IR模型小鼠随机分为:高脂饲料(HFD)组、高脂+溶剂(HFD+CMC-Na)组、高脂+牛蒡子苷组(其中HFD+ARC100组给予ARC 100 mg/kg,HFD+ARC200组给予ARC 200 mg/kg)。同时选取正常小鼠普通饲料饲养,设为ND组。ARC灌胃10周后,血清学检测小鼠血脂和血糖水平;苏木精-伊红染色和Masson染色检测心肌形态和纤维化程度;实时荧光定量PCR和蛋白质免疫印迹法检测心肌胶原蛋白(Collagen)Ⅰ、CollagenⅢ、AU碱基富集区RNA结合因子1(AUF1)、转化生长因子(TGF)-β1、Smad3的mRNA和蛋白表达。结果与ND组比较,HFD组体重、空腹血糖、空腹胰岛素(FIN)、胰岛素抵抗指数(HOMA-IR)、甘油三酯、总胆固醇、低密度脂蛋白水平显著升高(P<0.05),心肌胶原纤维增多,CollagenⅠ、CollagenⅢ、AUF1、TGF-β1、Smad3的mRNA和蛋白表达显著增加(P<0.05)。与HFD组比较,ARC干预后HFD+ARC200组体重、空腹血糖、HOMA-IR、甘油三酯、总胆固醇、低密度脂蛋白水平均显著下降(P<0.05),心肌胶原纤维减少,CollagenⅠ、CollagenⅢ、AUF1、TGF-β1、Smad3的mRNA和蛋白表达显著下降(P<0.05)。结论ARC能调节糖脂代谢减轻IR,减少心肌胶原分泌,改善心肌纤维化,其机制可能与抑制AUF1、TGF-β1/Smad3信号有关。Objective To explore the effects of arctiin(ARC)on glucolipid metabolism and myocardial fibrosis in insulin-resistant mice.Methods C57BL/6J mice were fed with high-fat diet to establish a model of insulin resistance(IR).The modeled mice were randomly divided into a high-fat diet(HFD)group,a HFD+CMC-Na group,a HFD+ARC100 group(100 mg/kg ARC)and a HFD+ARC200 group(200 mg/kg ARC).Meanwhile,mice fed with normal diet was set as an ND group.After administration of ARC for 10 weeks,blood lipid and glucose were measured.Then,hematoxylin-eosin staining and Masson staining were used to detect morphological changes and myocardial fibrosis.The expression of CollagenⅠ,CollagenⅢ,ARE/poly(U)-binding/degradation factor(AUF)1,transforming growth factor(TGF)-β1/Smad3 mRNA and protein was detected by RT-qPCR and Western blot.Results Compared with the ND group,remarkable increases were found in body weight,fasting blood glucose,fasting insulin(FIN),homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride,total cholesterol and low density lipoprotein in the HFD group(P<0.05);myocardial collagen fibers increased;and the expression of CollagenⅠ,CollagenⅢ,AUF1,TGF-β1 and Smad3 mRNA and protein enhanced(P<0.05).Compared with the HFD group,ARC treatment resulted in remarkable decreases in body weight,fasting blood glucose,HOMA-IR,triglyceride,total cholesterol and low density lipoprotein in the HFD+ARC200 group(P<0.05);reduced myocardial collagen fibers,and decreased expression of CollagenⅠ,CollagenⅢ,AUF1,TGF-β1,and Smad3 mRNA and protein(P<0.05).Conclusions Arctiin can regulate glucolipid metabolism,ameliorate insulin resistance,reduce myocardial collagen secretion,and improve myocardial fibrosis,which may be associated with inhibition of the AUF1 and TGF-β1/Smad3 pathway.

关 键 词：牛蒡子苷 AUF1 TGF-β1/Smad3 胰岛素抵抗 心肌纤维化 

分 类 号：R329.21[医药卫生—人体解剖和组织胚胎学]