抗骨质疏松治疗的最佳他汀类药物及剂量选择的动物实验研究

Animal experiments of optimal statins drugs and doses of anti-osteoporosis treatment

目的探索具有最佳抗骨质疏松作用的他汀药物种类和药物剂量,为进一步研究他汀药物同时发挥抗骨质疏松和调脂作用提供基础。方法 40只12月龄新西兰白兔通过双侧卵巢切除和泼尼松龙诱导8周建立骨质疏松症模型,随机分为四组:生理盐水(normal saline,NS)组,瑞舒伐他汀(rosuvastatin,RSV)组,辛伐他汀(simvastatin,Sim)组,阿仑膦酸钠片(Alendronate,ALN)组。RSV组和Sim组按药物浓度梯度分为五个小组。定期测量白兔股骨骨密度(bone mineral desity,BMD)和骨钙素(bone gamma-carboxyglutamic-acid-containing proteins,BGP)、抗酒石酸酸性磷酸酶5b(tartrateresistant acid phosphatase 5b,TRACP-5b)值。结果8周末BMD较0周时明显降低(P<0.05)。12、24和36周末,RSV组、Sim组和ALN组比NS组BMD、BGP水平明显升高,TRACP-5b水平显著降低(P<0.01),并且RSV组与ALN组指标接近(P>0.05)。RSV组内中以60 mg/(kg·d)喂养时,BMD、BGP较其他组明显升高。结论他汀类药物具有抗骨质疏松的作用,效果接近唑来膦酸;亲水性瑞舒伐他汀比疏水性他汀药物作用更佳;并且剂量在60 mg/(kg·d)时效果更好。

Objective To explore the specie and dose of statin who has the best anti-osteoporotic effects,providing the foundation for further study of statins playing the role of anti-osteoporosis and regulating blood lipids.Methods 40 12-month-old New Zealand white rabbits by bilateral ovariectomy and prednisolone-induced for 8 weeks are randomly divided into four groups：normal saline group（NS）,rosuvastatin group（RSV）,simvastatin group（Sim）,Alendronate group（ALN）.RSV and Sim are divided into five groups by the dose gradient 20,40,60,80 and 100 mg/（kg·d）.White rabbit femur bone mineral density（BMD）,bone gamma-carboxyglutamic-acid-containing proteins（BGP）and tartrateresistant acid phosphatase 5b（TRACP-5b）are measured at the 0,8th,12 th,24th,36 th weekends.Results Compared with 0weekend,the rabbits BMD significantly reduced at 8th weekend（P〈0.05）.Comparing RSV,Sim and ALN to NS,the BMD and BGP levels are significantly increased,TRACP-5b level are significantly reductive（P〈0.01）,and RSV group and ALN datas are close（P〉0.05）.In the RSV groups feeded by 60 mg/（kg·d）,BMD and BGP are significantly higher than other groups after 12 weeks.Conclusion Statins have anti-osteoporosis effects,closing to zoledronic acid;hydrophilic statin rosuvastatin is more effective than the hydrophobic;and has better results at the dose 60 mg/（kg·d）.