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依西酞普兰和卡比多巴对 Wistar 大鼠骨标志物的影响:一项初步的实验研究。

Effect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study.

机构信息

Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.

Pharmaceutical Medicine, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.

出版信息

J Bone Miner Metab. 2019 Jan;37(1):36-42. doi: 10.1007/s00774-018-0908-1. Epub 2018 Jan 29.

Abstract

In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined. Our results indicated that escitalopram adversely affected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the effects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for effects on resorption seem unrelated to gut serotonin. The promising effects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations.

摘要

鉴于肠道和大脑中血清素对骨骼的作用相反,Wnt β/catenin 通路在成骨细胞增殖中的关键作用,以及选择性 5-羟色胺再摄取抑制剂抗抑郁药对骨骼的影响存在争议,本研究旨在探讨艾司西酞普兰单用及与卡比多巴(阻断肠道来源的血清素)联合对雄性 Wistar 大鼠骨转换标志物和 Wnt 信号转导及 micro-CT 的影响。艾司西酞普兰(2.0mg/kg,口服)和卡比多巴(10mg/kg,口服)每天给药 40 天,之后测定骨形成标志物(降低的:DKK-1、骨硬化蛋白;增加的:碱性磷酸酶)和骨吸收标志物(核因子 κB 受体激活剂配体、抗酒石酸酸性磷酸酶 5b)。结果表明,艾司西酞普兰通过降低骨形成和增强骨吸收对骨骼产生不利影响。此外,艾司西酞普兰对骨形成的影响可能通过肠道血清素介导,而对吸收的影响机制与肠道血清素无关。本研究观察到卡比多巴对骨形成有积极影响,这为该药物的应用开辟了令人兴奋的可能性,需要进一步研究。

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