文献类型：期刊文章

作　　者：卢希[1] 袁梽漪[1] 姜敬非[1] 雷帆[2] 冯天师[1] 王玉刚[3] 王欣佩[1] 邢东明[1] 李俊[4] 杜力军[1]

机构地区：[1]清华大学生命科学学院药物药理实验室,中国北京100084 [2]清华大学药学院,中国北京100084 [3]德州大学MD Anderson癌证中心,神经-肿瘤学系,美国德克萨斯休斯顿77030 [4]江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室,中国江西南昌330006

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：National Natural Science Foundation of China(Grant No.81374006,81073092 and 90713043)

年　　份：2017

卷　　号：26

期　　号：4

起止页码：237-254

语　　种：中文

收录情况：CAB、CAS、CSCD、CSCD2017_2018、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be reduced via BBR treatment, which antagonizes HSP70-TNFa to regulate the body temperature alteration. In cold stress, however, the molecular mechanism of BBR-induced inhibition of hypothermia remains unclear. Therefore, we studied whether BBR promoted uncoupling protein 1 （UCP1, a crucial protein of thermogenesis） expression and its mechanism under cold stress. Wild type mice and Ucpl-/- mice were used for the in vivo experiments, and primary brown adipocytes and brown adipocytes HIB-1B were used for the in vitro studies. The cold stress was set at 4℃. The results showed that at 4℃, the body temperature of mice was decreased. BBR effectively inhibited this hypothermia. Simultaneously, Ucpl expression in brown adipose tissue （BAT） cells was significantly increased, and BBR promoted Ucpl expression. However, in Ucpl-knockout mice, the effect of BBR on hypothermia disappeared during cold stress, indicating that the main target for BBR regulation of body temperature was Ucpl. Further studies showed that the transcriptional response element NFE2 （nuclear factor erythroid-derived 2） in the upstream of the Ucpl promoter region contributed to the positive regulatory role on Ucpl expression at lower temperature. BBR could bind to the sequence of NFE2 response element in a temperature-dependent manner. Increased affinity of BBR binding to NFE2 response element in cold stress significantly strengthened and enhanced the expression of Ucpl. This work was important for understanding the role of BBR on thermogenesis in BAT, body temperature regulation and temperature tolerance under cold conditions.

关 键 词：BERBERINE Ucpl  THERMOGENESIS Cold stress  NFE2  

分 类 号：R284[中药学类]