Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway.

摘要: // Hongyan Wei 1, 2, * , Ting Zhou Boyu Tan 2 Lei Zhang 3 Mingming Li 1 Zhijun Xiao and Feng Xu Fengxian Hospital, Southern Medical University, Shanghai, China Hunan Provincial People’s Normal Changsha, Joint Research Center for Translation Medicine, East These authors have contributed equally to this work Correspondence to: Xu, email: andrewfxu1998@gmail.com Keywords: chronic unpredicted mild stress(CUMS), depression, repaglinide, drug-metabolizing enzymes (DMEs), glucocorticoid adrenergic signaling pathway Received: March 29, 2017      Accepted: April 24, Published: May 15, 2017 ABSTRACT Chronic stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, underlying mechanism is not clear. In we studied explored role regulating drug metabolizing (DMEs) GK rats BRL 3A cells. The plasma cortisol epinephrine levels were increased, meanwhile repaglinide altered significantly model rats. Forty-nine genes liver displayed significant difference comparing control differentially expressed enriched metabolism steroid hormone biosynthesis significantly, Nr1i3 matched 335 connectivity genes. CAR Ugt1a1 protein expression enhanced mRNA Nr1i2 increased 4 times respectively with dexamethasone (DEX) 8-Br-cAMP co-treatment PXR was up-regulated, too. However, RU486 reversed up-regulated effect. receptor agonists had little impact on DMEs 3A. Our data suggested that CUMS-induced might up-regulate via pathway, accelerate fate spontaneous diabetes