Irisin对老龄性骨质疏松小鼠骨代谢的影响及机制研究

Effects of Irisin on Bone Metabolism of Mice with Senile Osteoporosis and Related Mechanisms

目的探讨Irisin对老龄性骨质疏松小鼠骨代谢的影响及其机制。方法20只18月龄C57BL/6J小鼠按体重分为对照组(n=10)和实验组(n=10),10只6周龄C57BL/6J小鼠作为年轻组(n=10)。实验组按2μg的剂量尾静脉注射Irisin,对照组和年轻组注射等量生理盐水,每周3次,连续注射12周。检测骨代谢相关生化指标,Micro CT分析股骨形态学指标。采用qRT-PCR检测Irisin对骨髓间充质干细胞(BMSCs)成骨和成脂基因表达的影响。结果与年轻组比较,对照组和实验组的血钙和血碱性磷酸酶(ALP)浓度显著降低(P<0.05);与对照组比较,实验组的血ALP水平显著升高(P<0.05)。与年轻组比较,对照组和实验组的骨小梁相对骨体积(Tb.BV/TV)、骨密度(BMD)和皮质骨厚度显著降低,骨内膜周长显著升高(P<0.05);对照组的骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)显著降低,骨小梁间隙(Tb.Sp)显著升高(P<0.05)。与对照组比较,实验组Tb.BV/TV、Tb.N、Tb.Th和BMD明显升高,Tb.Sp显著降低(P<0.05)。Irisin能使BMSCs的成骨相关基因表达显著上调,成脂相关基因表达显著下调(P<0.05)。结论Irisin促进骨合成代谢并缓解老龄小鼠股骨骨质疏松,可能原因是促进BMSCs成骨基因的表达,抑制成脂基因的表达。

Objective To investigate effects of irisin on bone metabolism of mice with senile osteoporosis and related mechanisms.Methods A total of 2018-month old C57BL/6J mice were divided into control group(n=10)and experimental group(n=10)according to body weight.Another 6-week-old C57BL/6J mice were selected as young group(n=10).Experimental group was injected with 2μg irisin through tail vein,while control and young groups were injected with equivalent physiological saline,and all mice were treated for three times a week,and continuous injection was for 12 weeks.Biochemical indexes of bone metabolism were detected,and Micro CT was used to analyze histomorphology indexes of femurs.Effects of irisin on osteoblast and adipocyte expressions in bone marrow derived stroma cells(BMSCs)were tested by using quantitative reverse transcription-polymerase chain reaction(qRT-PCR)method.Results Compared with those in young group,Ca and alkaline phosphatase(ALP)concentrations in blood were significantly decreased in control and experimental groups(P<0.05);ALP concentration in experimental group was significantly increased compared with that in control group(P<0.05).Compared with those in young group,values of trabecular bone volume per tissue volume(Tb.BV/TV),bone mineral density(BMD)and cortical thickness(Ct.Th)were significantly decreased,while values of endosteal perimeter(Es.Pm)were significantly increased in control and experimental groups(P<0.05);values of trabecular number(Tb.N)and trabecular thickness(Tb.Th)were significantly decreased,while trabecular separation(Tb.Sp)was significantly increased in control group(P<0.05).Compared with those in control group,values of Tb.BV/TV,Tb.N,Tb.Th and BMD were significantly increased,while Tb.Sp value was significantly decreased in experimental group(P<0.05).Irisin could increase expressions of osteoblast-related genes and inhibit expressions of adipocyte-related genes(P<0.05).Conclusion Irisin promotes bone anabolism and relieves age-associated osteoporosis,and the possible cause is promoting expressions of osteoblast-related genes and inhibiting expressions of adipocyte-related genes in BMSCs.