辛伐他汀对大鼠骨髓基质干细胞Wnt信号通路相关因子表达的影响  

Simvastatin effects on correlation factor expression of Wnt signaling pathway in rat bone marrow stromal stem cells

作　　者：郑桓[1] 张柳[1,2] 田发明[2] 张辉[2] 穆树林[2] 

机构地区：[1]华北煤炭医学院研究生部,河北省唐山市063000 [2]华北煤炭医学院附属医院骨外科,河北省唐山市063000

出　　处：《中国组织工程研究与临床康复》2010年第23期4191-4194,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：河北省自然科学基金(C2006000580)资助;课题为辛伐他汀促进骨形成机制的研究~~

摘　　要：背景:辛伐他汀作为降脂类药物,具有一定的潜在促骨形成作用,并因此成为骨代谢领域的研究热点,但在体内试验中对其促进成骨的作用尚存争议。目的:观察辛伐他汀体内给药对大鼠骨量和骨髓基质干细胞增殖﹑分化的影响,及其在此过程中Wnt信号通路相关因子mRNA表达水平的变化。方法:6周龄雌性SD大鼠36只随机分成2组:对照组每天蒸馏水灌胃;实验组辛伐他汀灌胃20mg/(kg·d)。分别于给药后3,6,9周处死两组大鼠各6只,取左侧股骨行骨密度测定;取右侧股骨和胫骨骨髓细胞向成骨方向诱导培养,于细胞培养第16天检测碱性磷酸酶比活性、碱性磷酸酶染色;细胞培养第21天提取总RNA,采用Real-timeRT-PCR检测LRP-5、Axin2、β-catenin的mRNA的表达。结果与结论:辛伐他汀体内给药干扰3,6,9周后大鼠骨密度均无显著变化,体外培养骨髓基质干细胞所有检测基因mRNA水平、成骨分化能力与对照组相比差异均无显著性意义。辛伐他汀体内给药3,6,9周对大鼠骨量及骨髓基质干细胞的分化及LRP-5、Axin2、β-cateninmRNA表达无显著作用。BACKGROUND：As a lipid-lowering drug,simvastatin is getting more and more attention for its potential effects on bone formation in research of bone metabolism,but contradiction still exists when it is used for in vivo study.OBJECTIVE：To investigate the effects of simvastatin on bone mass,proliferation and differentiation of the cultured bone marrow stromal cells （BMSCs） in rats,as well as mRNA expression levels of some related factors of Wnt signaling pathway.METHODS：A total of 36 6-week-old female Sprague-Dawley rats were randomized into two groups.In the control group,the rats were treated with distilled water daily by gavage.In the experimental group,the rats were administrated 20 mg/kg simvastatin per day.Six rats from either group were sacrificed after the final administration at 3,6,9 weeks separately.The left femora were removed for the measurement of bone mineral density （BMD）.BMSCs derived from the right femora and tibiae were cultured in osteoblastic differentiation-induced medium.Alkaline phosphatase （ALP） activity measurement and ALP staining were performed on day 16.Real-time PCR was used to evaluate the mRNA expression levels of LRP-5,Axin2 and β-catenin on day 21 following total RNA was extracted.RESULTS AND CONCLUSION：After being administrated with simvastatin for 3,6 and 9 weeks,BMD of rats had no significant change.There were no significant differences in gene mRNA levels and osteogenic differentiation potential in BMSCs cultured in vitro compared with the control group.Administrated with simvastatin for either 3,6 or 9 weeks had no significant effect on BMD and the differentiation of BMSCs in rats,and on the expression levels of LRP-5,Axin2 and β-catenin mRNA.

关 键 词：辛伐他汀 骨密度 骨髓基质干细胞 REAL-TIMEPCR WNT/Β-CATENIN 

分 类 号：R394.2[医药卫生—医学遗传学]