Ho M-L, Chen Y-H, Liao H-J, Chen C-H, Hung S-H, Lee M-J, Fu Y-C, Wang Y-H, Wang G-J, Chang J-K
Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Eur J Clin Invest. 2009 Apr;39(4):296-303. doi: 10.1111/j.1365-2362.2009.02092.x.
Previous reports have indicated that statins could prevent bone loss in ovariectomized (OVX) rats and increase the expressions of osteogenic genes in cultured osteoblasts. In this study, we hypothesized that simvastatin might increase osteoblast number and protein expressions of osteogenic markers localized in bones in concomitance with the prevention of bone loss in OVX rats.
Fifty-four 3-month-old OVX and sham-operated (SHAM) female Sprague-Dawley rats were used. Simvastatin (10-20 mg kg(-1) day(-1)) was administrated orally for 6 weeks. Trabecular volume, osteoblast number and osteogenic proteins including BMP2, collagen type I and osteocalcin on bone sections obtained from lumbar vertebral body, distal femur and proximal tibia were measured.
The results showed that SHAM rats had significantly less trabecular bone volume and osteoblast number than that of OVX rats 6 weeks after operation. Oral simvastatin treatment (10-20 mg kg(-1) day(-1)) increased bone volume and osteoblast number in the distal femurs, proximal tibiae and vertebrae of OVX rats. Furthermore, the osteoblastic cells with immuno-stained BMP2, collagen type I and osteocalcin in vertebral bones were significantly increased by simvastatin treatment (20 mg kg(-1) day(-1)) in OVX rats.
This study demonstrates that simvastatin enhances the production of osteogenic proteins in bone and this effect may contribute to the prevention of bone loss in OVX rats.
先前的报告表明,他汀类药物可预防去卵巢(OVX)大鼠的骨质流失,并增加培养的成骨细胞中骨生成基因的表达。在本研究中,我们假设辛伐他汀可能会增加OVX大鼠骨骼中骨生成标志物的成骨细胞数量和蛋白质表达,同时预防骨质流失。
使用54只3个月大的OVX和假手术(SHAM)雌性Sprague-Dawley大鼠。口服给予辛伐他汀(10 - 20 mg kg⁻¹ 天⁻¹),持续6周。测量从腰椎椎体、股骨远端和胫骨近端获取的骨切片上的骨小梁体积、成骨细胞数量以及包括骨形态发生蛋白2(BMP2)、I型胶原蛋白和骨钙素在内的骨生成蛋白。
结果显示,术后6周,SHAM大鼠的骨小梁体积和成骨细胞数量明显少于OVX大鼠。口服辛伐他汀治疗(10 - 20 mg kg⁻¹ 天⁻¹)可增加OVX大鼠股骨远端、胫骨近端和椎骨的骨体积和成骨细胞数量。此外,辛伐他汀治疗(20 mg kg⁻¹ 天⁻¹)可使OVX大鼠椎骨中免疫染色显示BMP2、I型胶原蛋白和骨钙素的成骨细胞显著增加。
本研究表明,辛伐他汀可增强骨中骨生成蛋白的产生,这种作用可能有助于预防OVX大鼠的骨质流失。