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阿仑膦酸钠与视黄醇同时给药对大鼠卵巢切除诱导的骨组织形态计量学参数变化发展的影响。

Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats.

作者信息

Pytlik M, Kaczmarczyk-Sedlak I, Sliwiński L, Janiec W, Rymkiewicz I

机构信息

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

出版信息

Pol J Pharmacol. 2004 Sep-Oct;56(5):571-9.

Abstract

Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.

摘要

视黄醇是一种常用维生素,老年人尤其常用。阿仑膦酸钠是一种氨基双膦酸盐,是用于治疗绝经后女性骨质疏松症的强效抗吸收药物。阿仑膦酸钠和视黄醇经常同时使用。目前尚无关于阿仑膦酸钠与视黄醇相互作用的报道。本研究的目的是探讨阿仑膦酸钠和视黄醇同时给药对去卵巢大鼠骨重塑的影响。研究了长骨的组织形态计量学参数。实验在3个月大的Wistar大鼠上进行,分为7组:I组(C)——假手术对照大鼠;II组(OVX)——去卵巢对照大鼠;III组(OVX + ALN)——去卵巢大鼠 + 阿仑膦酸钠(3 mg/kg口服);IV组(OVX + R - 1)——去卵巢大鼠 + 视黄醇(700 IU/kg口服);V组(OVX + R - 2)——去卵巢大鼠 + 视黄醇(3500 IU/kg口服);VI组(OVX + ALN + R - 1)——去卵巢大鼠 + 阿仑膦酸钠(3 mg/kg口服) + 视黄醇(700 IU/kg口服);VII组(OVX + ALN + R - 2)——去卵巢大鼠 + 阿仑膦酸钠(3 mg/kg口服) + 视黄醇(3500 IU/kg口服)。通过口服灌胃每日给大鼠给药(早上给阿仑膦酸钠,下午给视黄醇),持续28天。研究了体重增加、骨量、胫骨、股骨和L - 4椎体的矿物质含量、右胫骨(类骨质宽度、骨膜和骨内膜横向生长、骨髓腔和皮质骨横截面积)和右股骨(骨骺和干骺端小梁宽度、骨骺软骨宽度)的组织形态计量学参数。双侧卵巢切除术导致成熟雌性大鼠出现骨质减少的骨骼变化。每日口服3 mg/kg剂量的阿仑膦酸钠可抑制去卵巢大鼠骨骼系统中由卵巢切除术引起的变化发展。视黄醇,尤其是每日以3500 IU/kg的剂量给药时,会加剧大鼠雌激素缺乏引起 的骨骼系统变化。与阿仑膦酸钠同时给药的视黄醇减弱了阿仑膦酸钠对去卵巢大鼠骨骼系统的抗吸收作用。

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