中文摘要：

目的：观察胰高血糖素样肽-1（GLP-1）及其受体激动剂exendin-4（EX-4）对体外培养大鼠骨髓间充质干细胞（BMSCs）增殖与成骨分化的影响。方法：取大鼠股骨和胫骨全骨髓,采用贴壁法分离BMSCs并传代至第三代,培养2d后分成4组：BMSC组、诱导成骨组（osteoblast induced medium,OIM组）和诱导加药组,诱导加药组细分为GLP-1（10^-9~10^-7 mol/L）或EX-4（10^-9~10^-7 mol/L）的不同浓度组,MTT法检测细胞增殖能力;测定碱性磷酸酶（ALP）活性;通过ALP染色及茜素红染色观察药物诱导BMSCs向成骨细胞分化、矿化的效果;采用RT-PCR方法检测ALP和Runx2成骨相关基因的表达情况。结果：与诱导对照组相比,GLP-1及EX-4各浓度处理组呈剂量依赖性显著促进细胞增殖（P〈0.05）;ALP染色与茜素红染色结果显示,对照组无显色或显色不明显,而GLP-1及EX-4组均有阳性显色。GLP-1及EX-4可以显著提高ALP活性,并提高Runx2、ALP的表达水平。结论：GLP-1及EX-4不仅能够直接促进BMSCs增殖,并促进其向成骨细胞分化,GLP-1及EX-4可能在骨重建中发挥重要的作用。

英文摘要：

AIM：To investigate the effects of GLP-1and GLP-1Ragonist exendin-4（EX-4）on the proliferation and differentiation of rat bone mesenchymal stem cells（BMSCs）.METHODS：BMSCs were isolated from rats＇ tibia and femur by the method of density gradient centrifugation and attachment were passaged to the three generation.4groups were divided after 2days cultivation,BMSC group,osteoblast induced medium（OIM）,and drug induced medium.In the drug induced medium,different concentration of GLP-1or EX-4（10^-9-10^-7 mol/L）were added to the media of the BMSC for the observation of cell proliferation（OD450）,differentiation（ALP staining）and mineralization（alizarin red staining for the observation of calcium nodule）of the BMSCs.RT-PCR was used to detect the expression of ALP,Runx2.RESULTS：Compared with the control group,GLP-1,EX-4treatment groups promoted cells proliferation in a dose-dependent manner（P〈0.05）;the ALP and alizarin red staining suggested,GLP-1,EX-4treatment groups were positive,the control group was weak stained or did not stain at all.ALP activity was improved,and the expressions of ALP and Runx2 were increased.CONCLUSION：The proliferation,differentiation and mineralization of the BMSCs are promoted directly by GLP-1and EX-4,which may play an important role in bone reconstruction.