仙灵骨葆胶囊干预糖尿病模型大鼠的骨代谢  

Bone metabolism in a rat model of diabetes mellitus intervened by Xianling Gubao Capsules

作　　者：焦颖华 包凯然 宋洁琼 邢磊 崔立华 高静媛 齐宁 刘香玉 Jiao Yinghua;Bao Kairan;Song Jieqiong;Xing Lei;Cui Lihua;Gao Jingyuan;Qi Ning;Liu Xiangyu(Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,Hebei Province,China;North China University of Science and Technology,Tangshan 063000,Hebei Province,China)

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

出　　处：《中国组织工程研究》2022年第32期5173-5178,共6页Chinese Journal of Tissue Engineering Research

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

摘　　要：背景:研究发现仙灵骨葆胶囊可改善骨代谢、防治骨质疏松,但是否对糖尿病并发的骨质疏松症具有预防作用或可能的机制却鲜有报道。目的:观察仙灵骨葆胶囊对糖尿病并发骨质疏松症大鼠的骨代谢以及相关成骨标志物因子Wnt3a、β-连环蛋白、骨形态发生蛋白2的影响并探讨其作用机制。方法:将36只雄性健康8周龄SD大鼠腹腔单剂量注射60 mg/kg链脲佐菌素建立糖尿病模型,建模成功后按随机原则分为模型组、仙灵骨葆组、阿仑膦酸钠组,每组12只,同时设正常组12只。仙灵骨葆组大鼠给予仙灵骨葆胶囊混悬液灌胃,阿仑膦酸钠组大鼠给予阿仑膦酸钠混悬液灌胃,正常组和模型组大鼠分别予等量双蒸水灌胃,均连续灌胃12周。给药期间每周测1次糖尿病成模大鼠的血糖值以确保其血糖水平> 16.7 mmol/L。治疗结束后应用双能X射线骨密度仪测量大鼠股骨、胫骨及全身骨密度;取各组大鼠右侧股骨行苏木精-伊红染色观察骨组织形态学变化;应用免疫组织化学和RT-PCR检测成骨标志物因子Wnt3a、β-连环蛋白、骨形态发生蛋白2的蛋白和mRNA表达。结果与结论:①与模型组相较,仙灵骨葆组大鼠的股骨、胫骨及全身骨密度均显著增加(P <0.05);②模型组大鼠骨组织中成骨标志物因子Wnt3a、β-连环蛋白、骨形态发生蛋白2的蛋白和mRNA表达量均显著下降(P<0.05);与模型组相较,仙灵骨葆组大鼠骨组织Wnt3a、β-连环蛋白、骨形态发生蛋白2的蛋白和m RNA表达量均显著增加(P <0.05),仙灵骨葆组与阿仑膦酸钠组比较,上述3项指标差异无显著性意义(P> 0.05);③结果证实,仙灵骨葆胶囊通过Wnt/β-连环蛋白信号通路介导对糖尿病大鼠骨代谢的保护作用。BACKGROUND:Xianling Gubao Capsules(a commonly used Chinese medicine in orthopedic surge ry) can improve bone metabolism and prevent osteoporosis;however,whether it has a preventive effect or a possible mechanism on osteoporosis complicated by diabetes has been ra rely repo rted.OBJECTIVE:To investigate the effects of Xianling Gubao Capsules on bone metabolism and related osteogenic marker factors Wnt3a,β-catenin and bone morphogenetic protein-2 in rats with diabetes mellitus complicated by osteoporosis and to explore their mechanisms of action.METHODS:Thirty-six male healthy 8-week-old Sprague-Dawley rats were treated with streptozotocin at a dose of 60 mg/kg to establish a diabetes mellitus model and were then randomly divided into model group,Xionling Guboo Capsule group and alendronate group,with 12 rats in each group.Another 12 normal rats were used as the normal group.Rats in the Xianling Gubao Capsule group and alendronate group were given Xianling Gubao Caps ule and alendronate sodium suspension by gavage for 12 weeks,respectively.Rats in the normal and model groups were gavaged with the same amount of double-distilled water for 12 weeks.Blood glucose level of model rats was measured once a week during the administration period to ensure the accuracy of the expe riment.Femur,tibia and systemic bone mineral density in each group were measured by dual energy X-ray absorptiometry.Hematoxylin-eosin staining was used to observe the morphological changes of the right femur in each group.Immunohistochemistry and RT-PCR were applied to detect the expression of osteogenic marker factors Wnt3a,β-catenin,and bone morphogenetic protein-2 at protein and mRNA levels.RESULTS AND CONCLUSION:Compared with the model group,the femur,tibia and systemic bone mineral density values of rats increased significantly in the Xianling Gubao Capsule group(P<0.05).The mRNA and protein expressions of Wnt3a,β-catenin,and bone morphogenetic protein-2 in bone tissues decreased significantly in the model group(P <0.05).While compared wit

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

分 类 号：R446[医药卫生—诊断学] R496[医药卫生—临床医学]