辛伐他汀对老年大鼠骨髓基质干细胞成骨和成脂分化的影响  

The effect of simvastatin on the differentiation of marrow stromal cells from aging rats

作　　者：刘铭[1] 朱振安[1] 汤亭亭[1] 王克敏[2] 

机构地区：[1]上海交通大学医学院附属第九人民医院骨科,上海200011 [2]上海交通大学医学院基础医学院生物化学和分子生物学教研室

出　　处：《中国骨质疏松杂志》2009年第6期414-422,共9页Chinese Journal of Osteoporosis

摘　　要：目的从细胞和基因水平探讨辛伐他汀对老年大鼠骨髓基质干细胞成骨和成脂分化的影响。方法18月龄雄性SD大鼠的骨髓基质干细胞进行成骨和成脂诱导培养,培养介质中加入辛伐他汀（10^-6、10^-7、10^-8mol/L和10^-9mol/L）,同时设溶剂对照组。成骨检测：碱性磷酸酶（ALP）染色和定量,茜素红矿化染色和定量,ALP和骨钙素（OC）基因分析;成脂检测：油红脂肪细胞染色和定量,脂蛋白脂酶（LPL）和过氧化物酶增殖活化受体（PPARγ2）基因分析。结果在含有低剂量地塞米松的成骨诱导条件下,辛伐他汀随浓度增加促进了细胞基质的矿化,增强了ALP的活性及染色,提高了ALP和OC的基因表达（若无地塞米松,辛伐他汀则无法单独诱导成骨,此结果未展示）;同时,辛伐他汀随浓度增加减弱了脂肪细胞的油红染色,抑制了LPL和PPARγ2的基因表达。显著性差异皆发生于10^-6mol/L和10^-7mol/L辛伐他汀组。结论辛伐他汀随浓度增加抑制了老年骨髓基质干细胞的成脂分化,并中等强度地促进了老年骨髓基质干细胞的成骨分化。这表明辛伐他汀具有促进骨合成代谢的作用,可以用于治疗常见的骨代谢疾病,如增龄性的骨质疏松症。Objective To assess the effect of simvastatin on osteoblastic and adipocytic differentiation of marrow stromal cells （MSCs） from aging rats. Methods MSCs from 18-month-old SD rats were cultured in osteogenesis or adipogenesis conditions. Simvastatin, including 10^-6, 10^-7, 10^-8 and 10^-9 mol/L, is added into culture medium. Osteogenesis test： alkaline phosphatase （ALP） activity and staining, gene expression of ALP and osteocalcin （OC）, mineralization staining. Adipogenesis test： Oil Red 0 staining gene expression of lipoprotein lipase （LPL） and peroxisome proliferator activated receptor （PPAR72） . Results Simvastatin, added into culture medium with a low dose of dexamethasone, enhanced ALP activity and staining, increased the gene expression of ALP and OC, and promoted mineralization in a dose-dependent fashion.. Simultaneously, simvastatin also decreased Oil Red 0 staining and inhibited the gene expression of LPL and PPARγ2 in a dose-dependent fashion. Significant effects were observed at 10^-6 and 10^-7 mol/L simvastatin （P 〈 0.05 ）. Conclusion These results indicate that simvastatin has anabolic effects on hone through the inhibition of adipocytic differentiation and the modest promotion of osteoblastic differentiation, suggesting that it could be used for the treatment of common metabolic bone diseases, such as aged osteoporosis.

关 键 词：辛伐他汀 老年 骨髓基质干细胞 成骨细胞 脂肪细胞 细胞分化 

分 类 号：R965[医药卫生—药理学]