基于PI3K/Akt通路研究利拉鲁肽对2型糖尿病骨质疏松大鼠的作用  

Effect of liraglutide on type 2 diabetic osteoporosis rats based on the study of PI3K/Akt pathway

作　　者：张莹[1] 周艳红[1] 李江雁[1] 赵建林[1] 吴苏豫[1] 熊承云 孙超[1] ZHANG Ying;ZHOU Yanhong;LI Jiangyan;ZHAO Jianlin;WU Suyu;XIONG Chengyun;SUN Chao(Xinxiang Central Hospital,Xinxiang 453000,Henan,China)

机构地区：[1]新乡市中心医院,河南新乡453000

出　　处：《中国骨质疏松杂志》2021年第7期985-989,共5页Chinese Journal of Osteoporosis

基　　金：河南省医学科技攻关计划联合共建项目(2018020214)。

摘　　要：目的基于磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(phosphateidylinositol-3 kinase/serine-threonine kinase,PI3K/Akt)通路研究利拉鲁肽对2型糖尿病性骨质疏松(type 2 diabetic osteoporosis,T2DOP)大鼠的影响。方法高脂高糖、腹腔注射30mg/kg链脲佐菌素(STZ)并摘除卵巢建立T2DOP大鼠模型,将大鼠随机分为模型组、利拉鲁肽组、利拉鲁肽+LY294002组;正常饲养大鼠作为正常组,每组10只。大鼠体重,空腹血糖,股骨组织形态,血清中骨保护素(OPG)、细胞核因子KB受体活化因子配基(RANKL)水平,骨密度,股骨组织中磷酸化-PI3K(p-PI3K)、PI3K、磷酸化-Akt(p-Akt)、Akt蛋白水平进行比较。结果模型组大鼠体重、FBG,血清中RANKL水平升高(P<0.05),血清中OPG水平、股骨组织骨密度,p-PI3K/PI3K、p-Akt/Akt蛋白水平降低(P<0.05);而利拉鲁肽组大鼠体重、FBG,血清中RANKL水平降低(P<0.05),血清中OPG水平、股骨组织骨密度,pPI3K/PI3K、p-Akt/Akt蛋白水平升高(P<0.05);利拉鲁肽添加PI3K抑制剂LY294002后逆转利拉鲁肽症状。结论利拉鲁肽激活PI3K/Akt通路实现对T2DOP大鼠骨质疏松的保护。Objective To study the effect of liraglutide on type 2 diabetic osteoporosis(T2DOP)rats based on the study of phosphatidylinositol-3 kinase/serine-threonine kinase(PI3K/Akt)pathway.Methods T2DOP rat model was established with high fat and high sugar intake,intraperitoneal injection of 30 mg/kg streptozotocin(STZ),and removal of the ovaries.The rats were randomly divided into model group,liraglutide group,and liraglutide+LY294002 group,and normal fed normal group,with 10 rats in each group.Body weight,fasting blood glucose,femoral tissue morphology,serum osteoprotegerin(OPG),nuclear factor KB receptor activator ligand(RANKL)levels,bone mineral density,femoral tissue phosphorylation-PI3K(p-PI3K),PI3K,phosphorylation-Akt(p-Akt),and Akt protein levels were compared.Results In the model group,body weight,FBG,and serum RANKL levels increased(P<0.05),serum OPG levels,femoral bone mineral density,p-PI3K/PI3K,and p-Akt/Akt protein levels decreased(P<0.05).In the liraglutide group,body weight,FBG,and serum RANKL levels decreased(P<0.05),and the serum OPG levels,femoral bone mineral density,and p-PI3K/PI3K,p-Akt/Akt protein levels increased(P<0.05).PI3K inhibitor LY294002 reversed the symptoms of liraglutide.Conclusion Liraglutide activates PI3K/Akt pathway to alleviate osteoporosis in T2DOP rats.

关 键 词：磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶通路 利拉鲁肽 2型糖尿病性骨质疏松 骨保护素 骨密度 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]