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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 peroxisome proliferator-activated receptor (PPARγ2), osteocalcin (OCN) and bone-specific alkaline phosphatase (BALP) in ovariectomized rats Loose relationship (PMOP) and possible mechanism of action. Methods 144 healthy female 3-month-old Wistar rats were divided into ovariectomized group and sham-operation group, and were given saline, pioglitazone 4 mg / (kg · d) or 20 mg / (kg · d) At different time points, the expression of PPARγ2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), the levels of OCN and BALP were detected by enzyme-linked immunosorbent assay (ELISA) . Results (1) PPARγ2 increased in a time-dependent manner in the two groups with different concentrations of pioglitazone, and the time-dependent decrease of OCN, BALP and BMD was found in ovariectomized rats. The difference was statistically significant (P <0.05, P < 0.01). (2) At the same time point, PPARγ2 increased in a dose-dependent manner in groups with different concentrations of pioglitazone, OCN, BALP and BMD decreased in a dose-dependent manner, and the ovariectomized rats were more obvious Statistical significance (P <0.05, P <0.01). Conclusion Pioglitazone may up-regulate the transcription of PPARγ2 gene and decrease the expression of OCN and BALP in osteoblasts, leading to osteoporosis.