吡格列酮对去卵巢大鼠过氧化物酶体增殖物激活受体γ2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
  
DOI:10.3969/j.issn.1006-7108.2015.02.007
中文关键词:  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
英文关键词:Pioglitazone  PPARγ2  OCN  BALP
基金项目:山西省自然科学基金(2012011039-2)
作者单位
谢小利1 吴迎爽2 朱亦堃3* 史书红3 李兴3 赵宝珍3 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 
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中文摘要:
      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4mg/(kg.d)或20mg/(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。
英文摘要:
      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-month-old female Wistar rats were selected and divided into ovariectomized group and sham operation group. The rats groups were gavaged normal saline, 4mg/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.
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