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游泳和下坡跑通过CN/NFAT信号途径对2型糖尿病小鼠骨吸收代谢的影响 被引量:6

Effects of Swimming and Downhill Running on Bone Absorption Metabolism in Type 2 Diabetic Mice via CN/NFAT Signal Pathway
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摘要 目的:探究游泳和下坡跑通过钙调磷酸酶(CN)/活化T细胞核因子(NFAT)途径对T2DM小鼠骨吸收代谢的影响。方法:采用6周高脂膳食和一次性注射链脲佐菌素(STZ)进行T2DM造模,成功后随机分为T2DM对照组(TC)、T2DM游泳组(TS)和T2DM下坡跑组(TD),另选C57小鼠为正常对照组(ZC)。T2DM小鼠继续高脂膳食,ZC小鼠饲以普通饲料。TS和TD小鼠分别进行8周游泳和下坡跑训练。末次训练24 h后处死小鼠并取材,应用Micro-CT、细胞原代培养、ELISA、RT-PCR及West-blotting等技术方法对骨组织形态计量学指标、OC数量、离子浓度、细胞因子m RNA和蛋白表达等进行检测。结果:TC组股骨中TRAF6、CN、Src-3、PLC、NFATc1、TRAP m RNA及胫骨中Src1和NFATc1蛋白表达上调(P<0.05),血清IP3和Ca2+浓度升高(P<0.05),BMM分化产生的OC总数量和≥10个核OC数量增多(P<0.01)。股骨远端松质骨和皮质骨骨组织形态计量学指标显著下降(P<0.05)。与TC比,TS组股骨中TRAF6、CN、PLC和TRAPm RNA及Src1蛋白表达下调,血清Ca2+浓度下降(P<0.05或P<0.01)。TD组股骨中TRAF6、CN、Src-3、PLC、NFATc1和TRAPm RNA及胫骨中Src1和NFATc1蛋白表达下调,血清IP3和Ca2+浓度下降(P<0.05)。OC总数量和≥10个核OC数量显著减少(P<0.05),松质骨和皮质骨骨组织形态计量学指标显著改善(P<0.05)。与TS比,TD组股骨中TRAF6、Src-3、PLC和TRAP m RNA表达下调及血清IP3和Ca^(2+)浓度下降(P<0.05),OC总数量(P<0.05)下降,松质骨BS/TV增加(P<0.05)。结论:T2DM小鼠骨吸收增强。下坡跑通过抑制T2DM小鼠骨中CN/NFAT途径,减少OC数量,降低骨吸收,改善骨组织形态结构,且其作用效果优于游泳。 Objective:The purpose of this study was to explore the effect of swimming and downhill running on bone resorption and metabolism in T2DM mice through calcineurin(CN)/activated T-cell nuclear factor(NFAT)pathway.Methods:Six-week high-fat diet and one-time injection of streptozotocin(STZ)were used to make T2DM models.After it,the mice were randomly divided into T2DM control group(TC),T2DM swimming group(TS)and T2DM downhill running group(TD),C57 mice were selected as normal control group(ZC).T2DM mice continued to have a high-fat diet and mice of ZC group were fed normal diets.The mice of TS and TD group were trained for 8 weeks swimming and downhill running.After 24 hours of the last training,the mice were sacrificed and each bone samples were harvested.Microscopy,primary cell culture,ELISA,RT-PCR,and West-blotting techniques were used to measure bone histomorphometry,OC number,ion concentration,mRNA and protein expression of cytokine were detected.Results:The expressions of TRAF6,CN,Src-3,PLC,NFATc1,TRAP mRNA and Src1,NFATc1 protein were up-regulated in TC group(P<0.05),and the concentrations of IP3 and Ca2+were increased(P<0.05).The total number of OC and the number of≥10 nuclear OCs were increased(P<0.01).Histological indicators of cancellous bone and cortical bone were significantly decreased(P<0.05).Compared with TC,the expression of TRAF6,CN,PLC,TRAP mRNA and Src1 protein in TS group were down-regulated,and Ca2+concentration was also decreased(P<0.05 or P<0.01).The expression of TRAF6,CN,Src-3,PLC,NFATc1,TRAP mRNA and Src1,NFATc1 protein were down-regulated in the TD group,and the IP3 and Ca2+concentrations were also decreased(P<0.05).The total number of OC and≥10 nuclear OC were significantly decreased(P<0.05),and histomorphometric indexes of cancellous bone and cortical bone were significantly improved(P<0.05).Compared with TS,the expression of TRAF6,Src-3,PLC,TRAP mRNA were down-regulated and the concentration of IP3 and Ca2+were decreased(P<0.05).The total number of OC decreased(P<0.05)and the BS/TV of cancellous bone were increased(P<0.05).Conclusion:The bone resorption of T2DM mice was enhanced.Downhill running inhibited the CN/NFAT pathway in bone of T2DM mice,reduced the number of OC,decreased the bone resorption,and improved the morphological structure of bone,and its effect was better than swimming.
作者 陈祥和 李世昌 孙朋 陈爱国 马涛 牟其林 CHEN Xiang-he;LI Shi-chang;SUN Peng;CHEN Ai-guo;MA Tao;MOU Qi-lin(Yangzhou University,Yangzhou 225127,China;East China Normal University,Shanghai 200241,China;Qilu Normal University,Jinan 250200,China;Guiyang University,Guiyang 550000,China)
出处 《中国体育科技》 CSSCI 北大核心 2018年第4期113-119,145,共8页 China Sport Science and Technology
基金 江苏省高等学校自然科学研究面上项目(17KJB180017)
关键词 运动 CN/NFAT 2型糖尿病 破骨细胞 骨吸收 骨组织形态计量学 exercises CN/NFAT type 2 diabetes mellitus osteoclast bone resorption bone tissue morphology metrology
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