阿托伐他汀对骨髓基质细胞增殖及向成骨细胞分化的影响

Effect of Atorvastatin on Proliferation and Differentiation of Osteoblasts Derived from Bone Marrow Mesenchymal Cells

目的比较不同浓度的阿托伐他汀对小鼠骨髓基质细胞向成骨细胞分化、矿化成骨的影响。方法分别将10^-8、10^-7、10^-6mol／L的阿托伐他汀和空白药物加入传代培养的小鼠骨髓基质细胞，通过细胞形态学观察、细胞增殖率检测、碱性磷酸酶（ALP）检测和钙结节染色，比较药物在成骨细胞分化过程中对细胞增殖和分化的影响。结果阿托伐他汀可以剂量依赖性方式抑制骨髓基质细胞的增殖，10^-7mol／L组和10^-6mol／L组较明显（均P〈0．05）。阿托伐他汀可以提高骨髓基质细胞ALP活性，培养10～22d，10^-7mol／L组和10^-6mol／L组ALP活性高于对照组和10^-8mol／L组（均P〈0．05）。矿化成骨染色显示在培养26d后，10^-6mol／L组染色明显深于其它各组。结论阿托伐他汀可促进骨髓基质细胞来源的成骨细胞的分化，抑制了细胞增殖，促进骨结节钙化。

Objective To compare the effect of artovastatin on cell proliferation and differentiation of cultured murine bone marrow-derived osteoblasts in vitro. Methods Osteogenetic culture medium containing different concentrations of atorvastatin （10^- 6, 10^- 7, 10^- 8 mol/L and control） were added in the murine bone marrow cell subculture. The proliferation of the stromal cells was observed, and alkaline phosphatase （ALP） staining and examination were done to check the differentiation ability of bone marrow cells. Alizarin red staining was performed to evaluate the mineralization of the osteoblasts in culture. Results Atorvastatin could inhibit the proliferation of bone marrow stromal cell in a dose-dependent manner, most significant in 10^-7 mol/L group and 10^- 6 mol/L group compared with control group and 10^- 8 mol/L group （all P〈0.05）. Atorvastatin enhanced the ALP activity of stromal cells. On 10th to 22nd day, ALP activity was stronger in 10^- 7 mol/L group and 10^- 6 mol/L group than in control group and 10^-8 mol/L group （all P〈0.05）. Bone nodule formation was very obvious at 26th day in 10^-6 mol/ L groups. Conclusion Atorvastatin may inhibit the proliferation, but stimulate the differentiation of osteoblasts derived from bone marrow stromal dells, accelerate the mineralization of osteoblasts and promote the maturation of bone nodules.