褪黑素对去卵巢大鼠细胞因子水平和RANKL/OPG比值及骨密度的影响

Effects of melatonin on cytokine levels,RANKL/OPG ratio and bone mineral density in ovariectomized rats

目的观察褪黑素对去卵巢大鼠细胞因子水平和RANKL/OPG比值及骨密度的影响。方法将32只3月龄的雌性大鼠随机分为4组,每组8只。A:假手术组(Sham组),B:去卵巢组(OVX组),C:去卵巢+β-雌二醇治疗组[487.5μg/(kg·d),OVX+E2组],D:去卵巢+褪黑素治疗组[50 mg/(kg·d),OVX+MEL组],药物治疗8周。治疗结束后,处死动物,取胫骨进行骨密度(bone mineral density,BMD)测定,对股骨进行细胞因子和基因表达分析。结果治疗8周时,OVX组胫骨骨密度较Sham组显著降低(P<0.05),而OVX+MEL组的胫骨骨密度较OVX组显著增高(P<0.05);OVX组RANKL/OPG比值较Sham组显著增高(P<0.05);OVX组股骨IL-17 A及IL-1β和TNF-α较Sham组显著增加(P<0.05),而IL-23较Sham组显著降低(P<0.05)。OVX+MEL组的股骨IL-17 A及IL-1β和TNF-α较OVX组显著降低,而IL-23较OVX组显著增加(P<0.05)。结论褪黑素可以通过降低RANKL/OPG比值,改善IL-23、IL-17 A、IL-1β和TNF-α细胞因子的表达来增加骨密度。

Objective To observe the effect of melatonin on the level of cytokines,RANKL/OPG ratio and bone mineral density in ovariectomized rats.Methods 323-month-old female rats were randomly divided into 4 groups:A:sham operation group(Sham group),B:ovariectomized group(OVX group),C:ovariectomized+β-estradiol treatment group[487.5μg/(kg·d),OVX+E2 group],D:ovariectomized+melatonin treatment group[50 mg/(kg·d),OVX+MEL group]for 8 weeks.After treatment,the animals were sacrificed,the tibia was taken for bone mineral density(BMD)determination,and the femurs were analyzed for cytokine and gene expression.Results After 8 weeks of treatment,the tibial bone mineral density in OVX group was significantly lower than that in Sham group(P<0.05),while the tibia bone mineral density in OVX+MEL group was significantly higher than that in OVX group(P<0.05).The ratio of RANKL/OPG in the OVX group was significantly higher than that in the Sham group(P<0.05);IL-17 A,IL-1βand TNF-αof femur in OVX group were significantly higher than those in Sham group,while IL-23 was significantly lower than that in Sham group(P<0.05).The IL-17 A,IL-1βand TNF-αof femur in OVX+MEL group were significantly lower than those in OVX group,while IL-23 was significantly higher than that in OVX group(P<0.05).Conclusion Melatonin can increase bone mineral density by reducing RANKL/OPG ratio and improving the expression of IL-23,IL-17 A,IL-1βand TNF-αcytokines.