辛伐他汀体外促进骨形成作用的初步研究

Effects of stmvastatin on bone formation in vitro

目的 研究辛伐他汀(Simvastatin)对成骨细胞分化、增殖及骨形成的作用。方法 用RPMI 1640培养液分别对水囊引产胎儿及新生大鼠颅顶骨进行组织培养,并将等量的胎儿或大鼠的颅顶骨骨组织分为实验组(辛伐他汀1μmol/L)和对照组,除动态观察比较不同培养液中成骨细胞的增殖状况外,将培养7d后的颅顶骨组织块制成半薄或超薄病理切片,于光镜下和电镜下进行形态学观察,并用测微尺测量新生骨组织厚度,记录成骨细胞数;同时,对留取的培养液测定其中的碱性磷酸酶(AKP)及骨钙素(BGP)的含量。结果 在培养过程中,可见实验组胎儿和新生大鼠颅骨成骨细胞生长活跃,数量多;对照组成骨细胞生长缓慢,数量少,可见大量成纤维细胞。培养7d后可见实验组胎儿及大鼠颅骨新生骨组织的厚度均明显高于对照组(P<0.01);其单位长度(0.3 mm)新生骨组织内成骨细胞数均明显高于对照组(P<0.01)。透射电镜下可见实验组成骨细胞处于活化状态,胞浆内有丰富的细胞器,少见破骨细胞,而对照组成骨细胞处于衰老状态,细胞器少见,可见大量破骨细胞。实验组培养液中AKP及BGP均明显高于对照组(P<0.01)。结论 辛伐他汀在体外实验中具有促进成骨细胞分化、增殖和促进新骨形成的作用;他汀类药物可作为预防、治疗骨质疏松症的有价值的候选药物。

Objective To investigate the biological effects of simvastatin on osteoblast differentiation and bone formation.Methods Equivalent calvarial bones taken from neonatal rats or aborted fetuses were cultured in RPMI 1640 medium which contained simvastatin( 1 μ mol/L) in experimental group during culture, osteoblast dif-ferentiation in different conditions was observed and compared. After culture, morphological changes were observed and osteoblasts were calculated under optical and electron microscope AKP and BGP levels in culture medium were assayed.Results Compared with control group,osteoblasts in the culture with simvastatin grew well,both the new bone volume and the number of osteoblasts were significantly large(P <0.01) ,the levels of AKP and BGP were el-evated, and,under electron microscope the osteoblasts were also in active state with few osteoclasts. Conclusion Simvastatin has promotive effects on osteoblast differentiation and bone formation in vitro. Statins may be a valuable drug for preventing and treating osteoporosis.