CAJ | 학술논문

目的通过建立饮食诱导的高脂小鼠的模型,观察过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)激动剂吡格列酮对肥胖小鼠的骨量变化的影响以及骨髓间充质干细胞(mesenchymal stem cell,MSCs)分化的情况,探讨PPARγ与MSCs分化之间的关系及可能的作用机制.方法建立饮食诱导的肥胖鼠模型,吡格列酮(10 mg·kg~(-1)·d~(-1))对肥胖小鼠进行灌胃,一个月后检测肥胖小鼠及灌胃组肥胖小鼠的葡萄糖耐量,骨密度及骨组织形态学,并取小鼠原代MSC进行培养,提取其RNA,利用实时定量PCR,检测在MSCs分化过程中成骨及成脂特异性基因的表达量.结果吡格列酮灌胃的肥胖小鼠胰岛素抵抗改善的同时,骨密度虽无明显改变,但骨组织形态学中成骨细胞周长百分率明显增加,原代MSCs的成骨分化基因的表达量明显增加而成脂基因明显下降.结论 PPARγ改善胰岛素抵抗的同时,促使MSCs向成骨细胞分化的能力增强,向脂肪细胞分化的能力下降,PPARγ除直接参与调节MSCs的分化外,还可能通过间接作用在MSCs的分化过程中起重要作用.
목적 통과건립음식유도적고지소서적모형,관찰과양화물매체증생물격활수체γ(peroxisome proliferator-activated receptor γ,PPARγ)격동제필격렬동대비반소서적골량변화적영향이급골수간충질간세포(mesenchymal stem cell,MSCs)분화적정황,탐토PPARγ여MSCs분화지간적관계급가능적작용궤제.방법 건립음식유도적비반서모형,필격렬동(10 mg·kg~(-1)·d~(-1))대비반소서진행관위,일개월후검측비반소서급관위조비반소서적포도당내량,골밀도급골조직형태학,병취소서원대MSC진행배양,제취기RNA,이용실시정량PCR,검측재MSCs분화과정중성골급성지특이성기인적표체량.결과 필격렬동관위적비반소서이도소저항개선적동시,골밀도수무명현개변,단골조직형태학중성골세포주장백분솔명현증가,원대MSCs적성골분화기인적표체량명현증가이성지기인명현하강.결론 PPARγ개선이도소저항적동시,촉사MSCs향성골세포분화적능력증강,향지방세포분화적능력하강,PPARγ제직접삼여조절MSCs적분화외,환가능통과간접작용재MSCs적분화과정중기중요작용.
Objective To explore the role of peroxisome proliferator-activated receptor γ(PPARγ) in the differentiation of MSCs in obesity mice.Methods Obese mice model was established by high-fat-diet,At sacrifice,BMD in the proximal femur was measured by dual-energy X-ray absorptiometry(DEXA).Bone histomorphometry was performed in proximal femur with undecalcified sections.The effect of pioglitazone on differentiation of mouse MSCs was assessed by gene expression analysis by real-time quantitative PCR. Results Insulin resistance was improved,Ob.S.Pm in pioglitazone treated mice were significantly greater than those of control mice.The mRNA level of Sox9,Dlx5 and Osterix was significantly higher while PPARγ was significantly lower in MSCs from pioglitazone treated mice versus control mice.Conclusion It is indicated that PPARγ may promote the gene expression of osteogenesis and diminish the expression of adipogenesis in the MSCs through indirect way.