Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Kralove, Czech Republic. gradosovai@ lfhk.cuni.cz
Pharmacology. 2012;89(1-2):37-43. doi: 10.1159/000335491. Epub 2012 Feb 1.
Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats.
Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing.
Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX.
Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis.
本研究旨在探讨氨氯地平对去势大鼠骨代谢的影响。
将 8 周龄大鼠分为三组。假手术对照组(SHAM)和去势对照组(ORX)给予标准实验室饮食(SLD)。去势加氨氯地平组(ORX+AML)给予 SLD 加氨氯地平 12 周。采用酶联免疫吸附试验检测血清 PINP、OPG 和 IGF-1 骨标志物浓度,骨匀浆 CTX-I、BAP 和 BMP-2 水平。采用双能 X 射线吸收仪测定骨密度(BMD)。对股骨进行生物力学测试。
与 SHAM 相比,ORX 中的骨标志物(CTX-I、BAP、BMP-2)更高。在 ORX+AML 中,与 ORX 相比,PINP、CTX-I、BAP、BMP-2 和 OPG 下降。与 SHAM 相比,ORX 中的 IGF-1 下降。在 ORX+AML 中,与 ORX 相比,IGF-1 增加。与 SHAM 相比,ORX 全身、腰椎和双侧股骨的 BMD 下降。与 ORX 相比,ORX+AML 全身 BMD 增加。三点弯曲试验显示,与 SHAM 相比,ORX 的最大载荷值下降。氨氯地平给药后,左股骨的最大载荷值增加。
氨氯地平能够减轻去势的负面影响,可能是预防骨质疏松的良好药物。