吡格列酮对去卵巢大鼠过氧化物酶体增殖物激活受体γ及骨钙素影响的实验研究  

Experimental study on the effect of pioglitazone on peroxisome proliferator activated receptorγ2 and osteocalcin in ovariectomized rats

作　　者：谢小利[1] 吴迎爽 朱亦堃[3] 史书红[3] 李兴[3] 赵宝珍[3] 

机构地区：[1] 山西医科大学研究生院,太原030001 [2] 河北省张家口第一医院内科,河北张家口075000 [3] 山西医科大学第二医院内分泌科,太原030001

出　　处：《中国骨质疏松杂志》2015年第2期158-162,共5页Chinese Journal of Osteoporosis

基　　金：山西省自然科学基金(2012011039-2)

摘　　要：目的观察吡格列酮对去卵巢大鼠过氧化物酶体增殖物激活受体(PPARγ2)、骨钙素(OCN)、骨特异性的碱性磷酸酶(BALP)的影响,探讨其与绝经后骨质疏松(PMOP)的关系及作用的可能机制。方法选用144只健康雌性3月龄Wistar大鼠作为研究对象,分为去卵巢组及假术手组,分别给予生理盐水、吡格列酮4 mg/(kg·d)或20 mg/(kg·d)灌胃,在干预的不同时间点采用逆转录PCR(RT-PCR)检测PPARγ2表达水平,酶联免疫吸附法测定OCN、BALP水平,DPX双能X线骨密度扫描仪检测实验动物骨量的变化。结果 (1)不同浓度的吡格列酮干预后两组大鼠PPARγ2呈时间依赖性上升,OCN、BALP、BMD呈时间依赖性下降,去卵巢组更明显,差异有统计学意义(P<0.05,P<0.01);(2)同一时间点不同浓度吡格列酮干预后两组大鼠PPARγ2呈剂量依赖性上升,OCN、BALP、BMD呈剂量依赖性下降,去卵巢组大鼠更明显,组间比较差异均有统计学意义(P<0.05,P<0.01)。结论吡格列酮可能通过启动PPARγ2基因的转录活性上调其表达,降低成骨指标OCN、BALP的表达,从而导致骨质疏松的发生。Objective To observe the effect of pioglitazone on PPARγ2,OCN,and BALP,and to explore the possible mechanism of pioglitazone and its relation to postmenopausal osteoporosis.Methods One hundred and forty-four healthy 3-monthold female Wistar rats were selected and divided into ovariectomized group and sham operation group.The rats groups were gavaged normal saline,4 mg/kg·d pioglitazone or 20 mg/kg·d pioglitazone.On different time point,RT-PCR was performed to determine the expression of PPAR γ2,enzyme linked immune assay was performed to detect the level of OCN and BALP,and DPX dual energy X-ray absorptiometry was used to detect the bone mass change of the experimental animals.Results 1） The expression of PPARγ2 showed a time-dependent increase after intervention with different doses of pioglitazone in two rat groups.OCN,BALP,and BMD showed a time-dependent decrease,and it was more significant in the ovariectomized group.The difference was statistically significant（P〈0.05,P〈0.01）.2） At the same time point,the expression of PPARγ2 showed a dose-dependent increase after intervention with different doses of pioglitazone in two rat groups.OCN,BALP,and BMD showed a dose-dependent decrease,and it was more obvious in the ovariectomized group.Statistical significance was found between the two groups（P〈0.05 P〈0.01）.Conclusion Pioglitazone may up-regulated PPARγ2 expression by initiating its transcription activity.It reduces the expression of OCN and BALP,resulting in the occurrence of osteoporosis.

关 键 词：吡格列酮 过氧化物酶体增殖物激活受体 骨钙素 骨特异性碱性磷酸酶 

分 类 号：R589[医药卫生—内分泌]