利拉鲁肽对2型糖尿病大鼠骨代谢及Wnt通路的影响  

Effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic rats with osteoporosis

作　　者：汤小斌[1] 潘春艳[1] 楼晔 Tang Xiaobin;Pan Chunyan;Lou Ye(Department of Orthopaedics,Jinhua People'$Hospital of Zhejiang Province,Jinhua 321001,China)

机构地区：[1]浙江省金华市人民医院骨科,321001

出　　处：《中华内分泌外科杂志》2019年第6期466-470,共5页Chinese Journal of Endocrine Surgery

基　　金：浙江省医药卫生科技计划项目(2019ky747)。

摘　　要：目的研究利拉鲁肽对2型糖尿病(T2DM)大鼠骨代谢及Wnt通路的影响。方法按随机数字表法将SD大鼠分为对照组、模型组、利拉鲁肽组,后两组采用高脂高糖饲料喂养及小剂量链腺佐菌素腹腔注射的方式建立T2DM模型,利拉鲁肽组在造模后给予0.6 mg/(kg.d)利拉鲁肽皮下注射,连续8周。检测3组大鼠胫骨的骨密度、钙磷含量、Wnt通路分子[Wnt3a、低密度脂蛋白受体相关蛋白5(low density lipoprotein receptor-related protein5,LRP5)连环蛋白(P-catenin)]表达量及血清中骨代谢指标[碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(osteocalcin,OC)、骨保护素(osteoprotegerin,OPG)A核因子kb受体活化因子配体(receptor activator of NF-KB ligand,RANKL)、抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TrACP)、I型胶原交联竣基端肽(cross-linked carboxy-terminal telopeptide of type 1 collagen,CTX-1)]的含量。结果模型组大鼠胫骨骨密度[左侧(0.158±0.024)vs(0.232±0.041)g/cm\右侧(0」52±0.027)vs(0.219±0.038)g/cm2,P<0.05)].胫骨中钙磷含量[(5.12±0.58)vs(5.93±0.74)mol/g.(2.93±0.41)vs(3.84±0.56)mol/g,P<0.05)]及Wnt3a、LRP5、0-catenin表达量[(0.29±0.06)vs(0.78±0・13)、(0.30±0.05)vs(0.73±0.14)、(0.38±0.06)vs(1.01±0」8),Pv0.05]、血清中ALP、OC、OPG含量均明显低于对照组[(40.27±7.52)vs(59.29±9.19)ng/ml、(252.45±42.95)vs(34i.28±52.39)pg/mL(0.40±0.06)vs(0.78±0.09)ng/ml,P<0.05],血清中RANKL、TrACP、CTX-1含量均明显高于对照组[(17.79±2.84)vs(12.46±2.09)pg/ml、(56.45±7.79)vs(41.38±8.19)Rmol/l、(19.26±3」4)vs(11.39±2.25)pg/ml,Pv0.05];利拉鲁肽组大鼠胫骨骨密度、胫骨中钙磷含量及Wnt3a、LRP5、p-catenin表达量、血清中ALP、OC、OPG含量均明显高于模型组,血清中RANKL、TrACP、CTX・l含量均明显低于模型组。结论利拉鲁肽能改善T2DM骨质疏松大鼠的骨密度及骨代谢,这一改善作用可能与激活Wtn通路有关。Objective To study the effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic osteoporosis rats.Methods SD rats were randomly divided into control group,model group and liraglutide group.The latter two groups were fed with high-fat and high-sugar diet and intraperitoneally injected with lowdose streptozotocin to establish type 2 diabetic model.Liraglutide group was subcutaneously injected with 0.6 mg/kg/d liraglutide for 8 weeks.Bone mineral density,calcium and phosphorus content,the expression of Wnt pathway molecule[Wnt3a,low density lipoprolein receptor-related protein 5(LRP5),p-catenin]and the contents of bone metabolism indicators[ALP,osteocalcin(OC),osteoprotegerin(OPG),receptor activator of nuclear factor-K B ligand(RANKL),tartrate-resistant acid phosphatase(TrACP),cross-linked carboxy-terminal telopeptide of type I collagen(CTX-1)]in serum were determined.Results The tibial bone mineral density[left(0.158±0.024)vs(0.232±0.041)g/cm2,right(0.152±0.027)vs(0.219±0.038)g/cm2,P<0.05),the content of calcium and phosphorus[(5.12±0.58)vs(5.93±0.74)mol/g,(2.93±0.41)vs(3.84±0.56)mol/g,P<0.05),the expression of Wnt3a,LRP5,p-catenin in tibia[(0.29±0.06)vs(0.78±0.13),(0.30±0.05)vs(0.73±0.14),(0.38±0.06)vs(1.01±0.18),Pv0.05],the content of ALP,OC and OPG in serum of model group were significantly lower than those of control group[(40.27±7.52)vs(59.29±9.19)ng/ml,(252.45±42.95)vs(341.28±52.39)pg/ml,(0.40±0.06)vs(0.78±0.09)ng/ml,P<0.05),and the contents of RANKL,TrACP and CTX-1 in serum were significantly higher than those of control group[(17.79±2.84)vs(12.46±2.09)pg/ml,(56.45±7.79)vs(41.38±8.19)|xmol/l,(19.26±3.14)vs(11.39±2.25)pg/ml,P<0.05];the tibial bone mineral density,the content of calcium and phosphorus,the expression of Wnt3a,LRP5,p-catenin in tibia,the content of ALP,OC and OPG in serum of liraglutide group were significantly higher than those of control group,and the contents of RANKL,TrACP and CTX-1 in serum were significantly lower than those of control group.Co

关 键 词：利拉鲁肽 2型糖尿病 骨质疏松 骨代谢 WNT通路 

分 类 号：R587.1[医药卫生—内分泌]