甜菜碱通过IGF-1R/β-catenin信号通路介导对2型糖尿病大鼠骨流失的保护作用

目的探讨甜菜碱(betaine,TCJ)对2型糖尿病大鼠骨量流失的影响,并探讨可能的机制。方法30只大鼠被随机分为对照组(CON)、模型组(MOD)及甜菜碱组(TCJ),每组10只,其中对MOD组和TCJ组建立2型糖尿病模型。随后TCJ组大鼠每天接受50 mg/kg甜菜碱治疗12周,待治疗结束后通过Micro-CT检测、HE染色切片以及蛋白质印迹检测。结果治疗12周后,与MOD组相比,三点弯曲试验、Micro-CT和HE染色切片结果显示TCJ组的大鼠骨小梁数量、骨强度和骨密度得到明显改善(P<0.05)。TCJ组大鼠最大载荷和弹性模量、骨密度(bone mineral density,BMD)、TV/BV、Tb.N、Tb.Th和Tb.Sp较MOD组明显改善(P<0.05)。和MOD组比较,TCJ组β-catenin表达水平明显上调,而p-IGF-1R、p-GSK-3β、p-β-catenin、IGF-1R和GSK-3β表达水平显著下调,比较差异有统计学意义(P<0.05)。结论甜菜碱通过IGF-1R/β-catenin信号通路介导对2型糖尿病大鼠骨流失起到保护作用。

Protective effect of betaine on bone loss in the type 2 diabetic rats is mediated by IGF-1R/β-catenin signal pathway

Objective To investigate the effect of betaine(TCJ)on bone loss in type 2 diabetic rats and explore the possible mechanisms.Methods Thirty rats were randomly divided into a control group(CON),a model group(MOD),and a betaine group(TCJ),10 in each group.Among them,type 2 diabetes models were established for MOD and TCJ group.Then TCJ group rats received 50 mg per day/kg betaine treatment for 12 weeks;after the treatment,they were detected by Micro-CT,HE stained sections and Western blot.Results After 12 weeks of treatment,compared with the MOD group,the result of the three-point bending test,Micro-CT and HE staining showed that the number of trabeculae,bone strength and bone density of the TCJ group were significantly improved(P<0.05).The maximum load and elastic modulus,BMD,TV/BV,Tb.N,Tb.Th and Tb.Sp of the TCJ group were significantly improved compared with the MOD group(P<0.05).Compared with the MOD group,the expression level ofβ-catenin in the TCJ group was significantly increased,while the expression levels of p-IGF-1R,p-GSK-3β,p-β-catenin,IGF-1R and GSK-3βwere significantly reduced(P<0.05).Conclusion Betaine mediates the protective effect on bone loss in type 2 diabetic rats through IGF-1R/β-catenin signaling pathway.