二甲双胍调控体外培养人甲状腺滤泡上皮细胞生长的研究  

Research of metformin regulating the growth of human thyroid follicular epithelial cells in vitro

作　　者：沈利兰[1] 孟作龙[1] 王晓敏[1] 吕娟琴[1] 何柏林 张立莹[1] SHEN Li-lan;MENG Zuo-long;WANG Xiao-min;Lü Juan-qin;HE Bai-lin;ZHANG Li-ying(Department of Endocrinology,The 1st People’s Hospital of Baiyin,Baiyin 730900,Gansu Province,China)

机构地区：[1]白银市第一人民医院内分泌科,甘肃白银730900

出　　处：《中国临床药理学杂志》2020年第19期3087-3090,3128,共5页The Chinese Journal of Clinical Pharmacology

基　　金：白银市第一人民医院院级科研立项课题资助项目(2016YQ-02)。

摘　　要：目的研究二甲双胍对人甲状腺滤泡上皮细胞生长增殖的作用,及其对腺苷酸活化蛋白激酶/西罗莫司靶蛋白(AMPK/mTOR)信号通路的影响。方法取对数生长期的Nthy-ori 3-1细胞分为A,B,C,D和E组。A组仅给予磷酸盐缓冲液;B,C和D组分别给予5.0,10.0和20.0 mmol·L^-1二甲双胍处理;E组给予20.0 mmol·L^-1二甲双胍+10.0μmol·mL^-1 compound C溶液处理。用噻唑蓝法检测细胞的增殖情况,用蛋白质免疫印迹法检测AMPKα1、AMPKα2和mTOR蛋白的表达水平。结果干预48 h后,A,B,C,D和E组组的增殖活性分别为1.62±0.12,1.48±0.14,1.20±0.12,0.75±0.10和1.53±0.17,AMPKα1蛋白表达量分别为0.48±0.05,0.57±0.07,0.79±0.10,1.07±0.11和0.18±0.02,AMPKα2蛋白表达量分别为0.58±0.07,0.73±0.10,0.86±0.12,1.17±0.12和0.27±0.04,mTOR蛋白表达量分别为1.78±0.23,1.51±0.16,1.33±0.10,1.12±0.14和1.45±0.17,A组的上述指标与B,C,D组比较,差异均有统计学意义(均P<0.05)。E组的上述与D组比较,差异均有统计学意义(均P<0.05)。结论二甲双胍能明显抑制人甲状腺滤泡上皮细胞的生长,其可能与激活AMPK信号通路,促使mTOR介导的蛋白质翻译通路受阻有关。Objective To study the effect of metformin on the growth and proliferation of human thyroid follicular epithelial cells and its effect on AMP-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)signal pathway.Methods Nthy-ori 3-1 cells were divided into A,B,C,D and E groups.A group was only given phosphate buffer saline.B,C and D groups were treated with 5.0,10.0 and 20.0 mmol·L^-1 metformin,respectively.E group received 20.0 mmol·L^-1 metformin+10μmol·mL^-1 compound C.The proliferation of cells was detected by thiazolyl blue method,and the expressions of AMPKα1,AMPKα2 and mTOR protein were detected by Western Blotting.Results After treatment for 48 h,the main indexes of A,B,C,D,E groups were compared,the proliferation activities were 1.62±0.12,1.48±0.14,1.20±0.12,0.75±0.10 and 1.53±0.17,AMPKα1 protein expressions were 0.48±0.05,0.57±0.07,0.79±0.10,1.07±0.11 and 0.18±0.02,AMPKα2 protein expressions were 0.58±0.07,0.73±0.10,0.86±0.12,1.17±0.12 and 0.27±0.04,m TOR protein expressions were 1.78±0.23,1.51±0.16,1.33±0.10,1.12±0.14 and 1.45±0.17.Compared with group B,C and D,the above indexes in group A were significantly different(all P<0.05).Compared with group D,the above indexes in group E were significantly different(all P<0.05).Conclusion Metformin can obviously inhibit the growth of human thyroid follicular epithelial cells,which may be related to the activation of AMPK signaling pathway and the blocking of m TOR mediated protein translation pathway.

关 键 词：二甲双胍 人甲状腺滤泡上皮细胞 腺苷酸活化蛋白激酶 西罗莫司靶蛋白 增殖 细胞周期 

分 类 号：R977.15[医药卫生—药品]