缺氧诱导因子抑制剂对去卵巢大鼠骨质疏松症治疗效果的研究

Effect of hypoxia inducible factor inhibitor on osteoporosis in ovariectomized rats

目的研究缺氧诱导因子抑制剂对卵巢切除(ovariectomized,OVX)雌性Sprague-Dawley大鼠的治疗效果,比较缺氧诱导因子抑制剂对骨密度的影响。方法在大鼠卵巢切除12周后,使用缺氧诱导因子抑制剂进行治疗。治疗8周后,在实验结束时将大鼠进行安乐死处理,获取大鼠血清、股骨和胫骨。通过生物力学测试,Micro-CT扫描和血清生化分析进行评估。结果与未给药的OVX大鼠相比,缺氧诱导因子抑制剂的全身给药显著降低了骨代谢指标Ⅰ型前胶原氨基末端前肽(type I collagen N terminal peptide,PINP)和Ⅰ型胶原羧基端肽(type I collagen carboxy-terminal peptide,CTX-I),增加了大鼠胫骨骨密度(bone mineral density, BMD),增强了股骨极限载荷、能量和刚度,差异比较有统计学意义(P<0.05)。结论缺氧诱导因子抑制剂能有效改善OVX诱导的骨质疏松症。

Objective We investigated the therapeutic effects of the administration of hypoxia inducible factor (HIF)inhibitor in ovariectomized (OVX)female Sprague-Dawley rats and compared the effects on bone mineral density.Methods After 12 weeks of ovariectomy,OVX rats were treated with hypoxia-inducible factor inhibitors.Eight weeks after treatment,rats were euthanized at the end of the experiment to obtain serum,femur and tibia.The effect of these treatments was evaluated by biomechanical tests, Micro-CT scans and serum biochemical analysis.Results Compared with untreated OVX rats,results and statistical analyses showed that systemic administration of HIF inhibitors significantly reduced bone metabolic markers type I procollagen N-terminal propeptide (PINP)and type I collagen carboxyl end peptide (CTX-I),increased rat tibia-bone density (BMD)and increased femur load,energy and stiffness,with statistically significant differences (P <0.05).Conclusion Hypoxia-inducible factor inhibitors could effectively improve OVX-induced osteoporosis.