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普萘洛尔对骨骼系统的影响是否取决于雌激素状态?

Do effects of propranolol on the skeletal system depend on the estrogen status?

机构信息

Department of Pharmacology, Medical University of Silesia, Katowice, Jagiellońska 4, PL 41-200 Sosnowiec, Poland.

出版信息

Pharmacol Rep. 2013;65(5):1345-56. doi: 10.1016/s1734-1140(13)71493-2.

Abstract

BACKGROUND

Propranolol, a nonselective β-adrenergic receptor antagonist, was reported to favorably affect the skeletal system in different animal models. The aim of the study was to investigate whether the effects of propranolol on the skeletal system depend on the estrogen status.

METHODS

The in vivo experiments were carried out on the following groups of mature female Wistar rats: sham-operated control rats, sham-operated rats receiving propranolol, ovariectomized (OVX) control rats, OVX rats receiving propranolol, OVX rats receiving estradiol, OVX rats receiving estradiol and propranolol. Propranolol hydrochloride (10 mg/kg po) and/or estradiol (0.1 mg/kg po) were administered daily for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. In vitro, effects of estradiol and propranolol on the formation of mouse osteoclasts and on the mRNA expression of genes related to osteoclastogenesis, bone formation and mineralization, as well as adrenergic and estrogen signalling in mouse osteoblasts were investigated.

RESULTS AND CONCLUSION

Propranolol exerted some favorable effects on the rat skeletal system in vivo, independently of the estrogen status. However, in vitro studies indicated a possibility of some antagonistic relations between the estradiol and propranolol effects.

摘要

背景

普萘洛尔是一种非选择性β-肾上腺素能受体拮抗剂,据报道,它能在不同的动物模型中对骨骼系统产生有益的影响。本研究旨在探讨普萘洛尔对骨骼系统的影响是否依赖于雌激素状态。

方法

在以下成熟雌性 Wistar 大鼠组中进行体内实验:假手术对照组大鼠、接受普萘洛尔的假手术组大鼠、去卵巢(OVX)对照组大鼠、接受普萘洛尔的 OVX 组大鼠、接受雌激素的 OVX 组大鼠、接受雌激素和普萘洛尔的 OVX 组大鼠。每日给予盐酸普萘洛尔(10mg/kg,po)和/或雌激素(0.1mg/kg,po),连续 4 周。检测骨量、矿物质和钙含量、宏观和组织形态计量学参数以及机械性能。体外研究了雌激素和普萘洛尔对小鼠破骨细胞形成以及与破骨细胞生成、骨形成和矿化以及骨细胞肾上腺素能和雌激素信号相关的基因的 mRNA 表达的影响。

结果与结论

普萘洛尔在体内对大鼠骨骼系统产生了一些有益的影响,而不依赖于雌激素状态。然而,体外研究表明雌激素和普萘洛尔的作用之间可能存在一些拮抗关系。

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