三种不同他汀类药物对去卵巢诱导骨质疏松大鼠骨密度的影响
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摘要
目的研究三种不同的他汀类药物对卵巢切除(OVX)雌性Sprague-Dawley大鼠的治疗效果,并比较其对大鼠骨密度的影响。方法在切除大鼠卵巢12周后,分别用生理盐水、阿托伐他汀、辛伐他汀和洛伐他汀治疗OVX大鼠。治疗2个月后,在实验结束时对大鼠进行安乐死,获取其血清和股骨。通过生物力学测试、Micro-CT扫描和血清生化分析评估治疗的效果。结果与未处理的OVX大鼠相比,辛伐他汀、阿托伐他汀和洛伐他汀的全身给药显著增加了血清成骨指标、骨密度(bone mineral density, BMD)和生物力学指标(P<0.05)。结论辛伐他汀、阿托伐他汀和洛伐他汀能有效改善OVX诱导的骨质疏松症。此外,经辛伐他汀治疗的动物的BMD、血清骨代谢指标和生物力学性能都显示了较好的结果。
Objective We investigated the therapeutic effects of the most important types of statin administered orally for 2 months to ovariectomized(OVX) female Sprague-Dawley rats and compared the effects on bone mineral density. Methods 12 months after ovariectomy, the OVX rats were treated with normal saline, atorvastatin, simvastatin and lovastatin. The osteoporotic animals were treated daily for 2 months and euthanized at the end of experiments. The effectiveness of these treatments was evaluated by biomechanical testing, micro-CT scan and serum biochemical analysis. Results The result and statistical analysis showed that systemic delivery of simvastatin, atorvastatin and lovastatin significantly increased serum osteogenic indexes, bone mineral density(BMD) and biomechanical properties in comparison with the untreated OVX rats(P<0.05). In all treatment groups, the SIM group achieved the best result. Conclusion It was concluded that simvastatin, atorvastatin and lovastatin could efficiently ameliorate the OVX-induced osteoporosis. Moreover, the simvastatin-treated animals showed the best result in terms of BMD, serum bone metabolic indexes and biomechanical properties.
Objective We investigated the therapeutic effects of the most important types of statin administered orally for 2 months to ovariectomized(OVX) female Sprague-Dawley rats and compared the effects on bone mineral density. Methods 12 months after ovariectomy, the OVX rats were treated with normal saline, atorvastatin, simvastatin and lovastatin. The osteoporotic animals were treated daily for 2 months and euthanized at the end of experiments. The effectiveness of these treatments was evaluated by biomechanical testing, micro-CT scan and serum biochemical analysis. Results The result and statistical analysis showed that systemic delivery of simvastatin, atorvastatin and lovastatin significantly increased serum osteogenic indexes, bone mineral density(BMD) and biomechanical properties in comparison with the untreated OVX rats(P<0.05). In all treatment groups, the SIM group achieved the best result. Conclusion It was concluded that simvastatin, atorvastatin and lovastatin could efficiently ameliorate the OVX-induced osteoporosis. Moreover, the simvastatin-treated animals showed the best result in terms of BMD, serum bone metabolic indexes and biomechanical properties.
引文
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[13] Park JB. The use of simvastatin in bone regeneration[J].Medicina Oral Patologia Oral Y Cirugia Bucal, 2009, 14(9): e485.
[14] Gradosova I, Zivna H, Palicka V, et al. Protective effect of atorvastatin on bone tissue in orchidectomised male albino Wistar rats[J]. European Journal of Pharmacology, 2012, 679(1-3): 144-150.
[15] Lin S, Huang J, Fu Z, et al. The Effects of Atorvastatin on the Prevention of Osteoporosis and Dyslipidemia in the High-Fat-Fed Ovariectomized Rats[J].Calcified Tissue International, 2015, 96(6): 541-551.
[16] Abdulmajeed S, Mohamed N, Soelaiman IN. Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis[J]. Evidence-Based Complementray and Alternative Medicine, 2012(4): 960742.
[17] Ibrahim NI, Khamis MF, Yunoh MFM, et al. Targeted Delivery of Lovastatin and Tocotrienol to Fracture Site Promotes Fracture Healing in Osteoporosis Model: Micro-Computed Tomography and Biomechanical Evaluation[J]. PLoS One, 2014, 9(12): e115595.
[2] Cole ZA, Dennison EM, Cooper C. Osteoporosis epidemiology update[J].Current rheumatology reports, 2008, 10(2): 92-96.
[3] Moshiri A, Sharifi AM, Oryan A. Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations[J].Clinical & Experimental Pharmacology & Physiology, 2016, 43(7): 659-684.
[4] Tsartsalis AN, Dokos C, Kaiafa GD, et al. Statins, bone formation and osteoporosis: hope or hype?[J]. Hormones, 2012, 11(2): 126-139.
[5] Oryan A, Alidadi S, Moshiri A, et al. Bone regenerative medicine: classic options, novel strategies, and future directions[J]. Journal of Orthopaedic Surgery & Research, 2014, 9(1): 18.
[6] Majima T, Komatsu Y, Fukao A, et al. Short-term effects of atorvastatin on bone turnover in male patients with hypercholesterolemia[J]. Endocrine Journal, 2007, 54(1): 145-151.
[7] Ogasawara R, Furuya Y, Sasaki H, et al. Effects of Oral Administration of Simvastatin on Bone Formation in Senile Osteoporosis Rat[J].Journal of Hard Tissue Biology, 2013, 22(4): 461-472.
[8] Oryan A, Bighamsadegh A, Abbasiteshnizi F. Effects of osteogenic medium on healing of the experimental critical bone defect in a rabbit model[J]. Bone, 2014, 63(3): 53-60.
[9] Wang Z, Ying L, Zhou F, et al. Effects of Statins on Bone Mineral Density and Fracture Risk: A PRISMA-compliant Systematic Review and Meta-Analysis[J]. Medicine, 2016, 95(22): e3042.
[10] Kharode YP, Sharp MC, Bodine PV. Utility of the Ovariectomized Rat as a Model for Human Osteoporosis in Drug Discovery[M]. Humana Press, 2008.
[11] Shah SR, Werlang CA, Kasper FK, et al. Novel applications of statins for bone regeneration [J]. Natl Sci Rev, 2015, 2(1): 85-99.
[12] Maritz FJ, Conradie MM, Hulley PA, et al. Effect of statins on bone mineral density and bone histomorphometry in rodents[J]. Arteriosclerosis, Thrombosis and Vascular Biology, 2001, 21(10): 1636-1641.
[13] Park JB. The use of simvastatin in bone regeneration[J].Medicina Oral Patologia Oral Y Cirugia Bucal, 2009, 14(9): e485.
[14] Gradosova I, Zivna H, Palicka V, et al. Protective effect of atorvastatin on bone tissue in orchidectomised male albino Wistar rats[J]. European Journal of Pharmacology, 2012, 679(1-3): 144-150.
[15] Lin S, Huang J, Fu Z, et al. The Effects of Atorvastatin on the Prevention of Osteoporosis and Dyslipidemia in the High-Fat-Fed Ovariectomized Rats[J].Calcified Tissue International, 2015, 96(6): 541-551.
[16] Abdulmajeed S, Mohamed N, Soelaiman IN. Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis[J]. Evidence-Based Complementray and Alternative Medicine, 2012(4): 960742.
[17] Ibrahim NI, Khamis MF, Yunoh MFM, et al. Targeted Delivery of Lovastatin and Tocotrienol to Fracture Site Promotes Fracture Healing in Osteoporosis Model: Micro-Computed Tomography and Biomechanical Evaluation[J]. PLoS One, 2014, 9(12): e115595.
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