二甲双胍对地塞米松作用下SD大鼠骨密度的影响及可能的机制

The effect of metformin on bone mineral density in SD rats treated with dexamethasone and the underlying mechanism

目的研究不同干预剂量和时间的二甲双胍对地塞米松作用下SD大鼠骨密度(bone mineral density,BMD)的影响及可能的机制。方法将72只雌性SD大鼠随机均分为对照组、地塞米松组和二甲双胍100(Met 100)、200(Met 200)、300(Met 300)、500(Met 500)mg组。除对照组外,各组均每周2次肌注5 mg/kg的地塞米松。各二甲双胍组每日给予相应剂量的二甲双胍灌胃1次。连续干预12周,每2周测体重1次并调整药物剂量。分别在干预前和干预后4、8及12周测大鼠BMD及体成分。实验结束时采集血样测定大鼠I型胶原C端肽(CTX-I)、骨钙素(OCN)等指标。结果干预前及干预4周,各组间的BMD比较差异无统计学意义(均P>0.05)。干预8周,地塞米松组BMD低于对照组(P<0.05);地塞米松组与各地塞米松联合二甲双胍组的BMD比较差异无统计学意义(均P>0.05)。干预12周,地塞米松组BMD仍低于对照组(P<0.05);Met 100组和Met 200组的BMD高于地塞米松组(均P<0.05);Met 300组和Met 500组的BMD与地塞米松组相比无差异(均P>0.05)。干预12周,对照组、Met 100组、Met 200组和Met 300组的CTX-I水平均低于地塞米松组(均P<0.05),而OCN水平均高于地塞米松组(均P<0.05)。结论二甲双胍可通过促进骨形成及抑制骨吸收改善地塞米松作用下SD大鼠的BMD,并与干预的时间和剂量有关。

Objective To investigate the effect of metformin(Met)administrated at different doses and duration on bone mineral density(BMD)in SD rats treated with dexamethasone(Dex)as well as the underlying mechanism.Methods Seventy-two 3-month-old female SD rats were randomly divided into six groups(n=12 per group):control group(Con),Dex group,Met 100 mg group(Met 100),Met 200 mg group(Met 200),Met 300 mg group(Met 300),Met 500 mg group(Met 500).Each group was injected with 5 mg/kg Dex intramuscularly twice a week except for Con group.Each Met group was given corresponding dose of Met by gavage once a day.These rats were treated with the experimental protocol for 12 weeks.The body weights were determined at the initiation of the experiment,and monitored once every two weeks to adjust the dosage of the drug.BMD and body composition were measured regularly.After 12 weeks,blood was collected to test indicators such as C-telopeptide of type I collagen(CTX-I)and osteocalcin(OCN).Results At the initiation of the experiment and after 4 weeks,there was no significant difference for BMD among each group(all P>0.05).After 8 weeks,the BMD in Dex group was lower compared with Con group(P<0.05),while there was no significant difference for BMD between Dex group and each Met groups(all P>0.05).After 12 weeks,compared with Dex group,the BMD in Con,Met100 and Met200 groups were higher(all P<0.05),while the BMD in Met300 and Met500 groups were not significantly different when compared with Dex group(all P>0.05).After 12 weeks,compared with Dex group,CTX-I was lower in Con,Met100,Met200 and Met300 group(all P<0.05),while OCN was higher(all P<0.05).Conclusion Our findings suggested that Met could improve the BMD of SD rats treated with Dex by stimulating bone formation and inhibiting bone absorption,which was associated with the dosage and treatment duration of Met.