仙灵骨葆胶囊对糖尿病骨质疏松大鼠β-catenin、Runx2、LRP5的影响  

Effect of Xianling Gubao Capsules on β-catenin,Runx2,LRP5 in Diabetic Rats with Osteoporosis

作　　者：焦颖华 郭倩 包凯然 邢磊 崔立华 齐宁 JIAO Yinghua;GUO Qian;BAO Kairan;XING Lei;CUI Lihua;QI Ning(Afiliated Hospital of North China University of Science and Technology,Tangshan 063000 Hebei,China;North China University of Science and Technology,Tangshan 063000 Hebei,China)

机构地区：[1]华北理工大学附属医院,河北唐山063000 [2]华北理工大学,河北唐山063000

出　　处：《中药新药与临床药理》2023年第2期156-162,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：2017年政府资助省级临床医学优秀人才项目(201705);2016年河北省中医药管理局项目(2016083)。

摘　　要：目的观 察糖尿病大鼠在仙灵骨葆胶囊的干预下,骨保护作用的发挥及仙灵骨葆胶囊对Wnt/β-连环蛋白(β-catenin)信号通路的作用,探讨仙灵骨葆胶囊在防治糖尿病骨质疏松中可能的作用机制。方法 雄性SD大鼠36只,左下腹腔注射链脲佐菌素(STZ,60 mg·kg^(-1)),建立糖尿病大鼠模型,随机分为模型组、仙灵骨葆组(250 mg·kg^(-1))、阿仑膦酸钠组(1 mg·kg^(-1)),每组12只;同时设正常组12只。治疗12周后,检测生化指标:空腹血糖(FBG)、血钙(BC)、血磷(BP)、碱性磷酸酶(ALP);酶联免疫吸附试验(ELISA)法测定骨碱性磷酸酶(BALP)、I型前胶原氨基末端前肽(PINP)、骨钙素(OCN)、骨保护蛋白(OPG)含量;检测大鼠骨密度(BMD)和股骨生物力学性能;逆转录聚合酶链反应(RT-PCR)法检测大鼠骨组织β-catenin、Runt相关转录因子2(Runx2)、低密度脂蛋白受体相关蛋白5(LRP5)mRNA的表达。结果 与正常组比较,模型组大鼠血清FBG、ALP、BALP、PINP、OPG水平升高(P<0.05),血清BC、BP、BMD、OCN水平降低(P<0.05),股骨生物力学性能下降(P<0.05),β-catenin、Runx2、LRP5 mRNA表达降低(P<0.05);与模型组大鼠比较,仙灵骨葆组能有效降低FBG、ALP、BALP、PINP、OPG水平(P<0.05),升高BC、BP、BMD、OCN含量(P<0.05),改善糖尿病骨质疏松大鼠股骨生物力学性能(P<0.05),升高β-catenin、Runx2、LRP5 mRNA的表达(P<0.05)。结论 仙灵骨葆胶囊可以改善糖尿病大鼠骨代谢,主要与调节Wnt/β-catenin信号转导通路有关,其中β-catenin、Runx2、LRP5 mRNA表达的增加对骨代谢有积极意义,在骨细胞分化方面有促进作用,具体表现在骨组织形态的改善及骨破坏减少,为糖尿病骨质疏松的防治提供了一条新思路。Objective To explore the possible mechanism of Xianling Gubao Capsules(XGC)on prevention and treatment of diabetes osteoporosis by observing the protective effect of XGC on diabetes rats and its effect on Wnt/β-catenin signaling pathway.Methods Thirty-six male SD rats were injected streptozotocin(STZ,60 mg·kg^(-1))intraperitoneally into the left lower abdominal cavity to establish the diabetes rat model,and were randomly divided into model group,XGC group(250 mg·kg^(-1)·d^(-1)),alendronate sodium group(1 mg·kg^(-1)·d^(-1)) and normal group,12 rats in each group.After 12 weeks of treatment,biochemical indexes including fasting blood glucose(FBG),blood calcium(BC),blood phosphorus(BP) and alkaline phosphatase(ALP) were detected.Bone alkaline phosphatase(BALP),aminoterminal propeptide of type I procollagen(PINP),osteocalcin(OCN)and osteoprotegerin(OPG)were determined by ELISA.Bone mineral density(BMD)and femoral biomechanical properties of rats were detected.The mRNA expressions of β-catenin,runt-related transcription factor 2(Runx2)and low-density lipoprotein receptor-related protein 5(LRP5)in rat bone tissue was detected by RT-PCR.Results Compared with normal group,serum FBG,ALP,BALP,PINP and OPG were increased in model group(P<0.05),while serum BC,BP,BMD and OCN were decreased(P<0.05).The biomechanical properties of femur and mRNA expressions ofβ-catenin,Runx2 and LRP5 were decreased(all P<0.05).Compared with model group,XGC could effectively reduce FBG,ALP,BALP,PINP,OPG(P<0.05),and increase BC,BP,BMD and OCN(P<0.05).Furthermore,XGC could improve the femoral biomechanical properties of diabetic rats with osteoporosis(P<0.05),and increase the mRNA expressions of β-catenin,Runx2,LRP5(P<0.05).Conclusion Xianling Gubao Capsules can improve bone metabolism in diabetic rats,which is mainly related to the regulation of Wnt/β-catenin signal transduction pathway and plays a role in bone protection.The increased mRNA expressions of β-catenin,Runx2 and LRP5 has a positive significance on bone metabolism and promo

关 键 词：仙灵骨葆胶囊 糖尿病 骨质疏松症 WNT/Β-CATENIN信号通路 Β-CATENIN RUNX2 LRP5 大鼠 

分 类 号：R285.5[医药卫生—中药学]