β-蜕皮甾酮通过调控β-catenin/BMP表达促进骨髓间充质干细胞分化治疗骨质疏松性骨折的作用机制  

The mechanism of β-ecdysterone in the treatment of osteoporotic fractures by regulating the expression of β-catenin/BMP and promoting the differentiation of bone marrow mesenchymal stemcells

作　　者：莫亚峰 周坤 王徐刚 熊振飞[1] 汤样华[1] Mo Yafeng

机构地区：[1]浙江中医药大学附属江南医院(杭州市萧山区中医院),311200 [2]浙江中医药大学附属第二医院,310005

出　　处：《浙江临床医学》2022年第9期1275-1278,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省中医药“新苗”人才计划项目(浙中医药[2021]1号);浙江省杭州市卫生科技计划(一般)项目(2018B029)。

摘　　要：目的探讨β-蜕皮甾酮通过调控β-catenin/BMP表达促进骨髓间充质干细胞分化治疗骨质疏松性骨折的作用及相关机制.方法选取3个月龄雌性TOPGAL小鼠,建立去卵巢骨质疏松小鼠模型,于去卵巢术后3个月建立胫骨骨折模型,随机均分为空白对照组、β-蜕皮甾酮组和仙灵骨葆组,每组10只,骨折术后第2天分别给予0.9%氯化钠溶液及相应药物灌胃治疗,连续灌胃治疗4周后取标本进行相关指标检测,比较各组小鼠血清雌二醇含量、胫骨影像学改变、病理组织学改变以及骨痂中骨形成蛋白-7(BMP-7)、β-连环蛋白(β-catenin)的表达水平.结果血清雌二醇含量检测结果显示,β-蜕皮甾酮组及仙灵骨葆组血清中雌二醇含量分别为(8.14±4.19)pg/mL、(12.23±4.92)pg/mL,均明显高于空白对照组(3.27±3.40)pg/mL(P<0.05).X线检测结果显示,空白对照组骨折端少量稀疏骨痂通过和少量外骨痂形成,骨折线可见;而β-蜕皮甾酮组和仙灵骨葆组骨折端外骨痂致密,部分髓腔再通,骨折线模糊.Micro-CT结果显示,空白对照组骨皮质厚度明显变薄,骨小梁稀疏;β-蜕皮甾酮组与仙灵骨葆组骨皮质厚度明显优于空白对照组,骨小梁结构相对紧密、均匀.HE染色发现,β-蜕皮甾酮组和仙灵骨葆组小鼠骨小梁数量、密度均得到明显改善,骨痂形状更为规则,与骨皮质贴合程度更高,其中以β-蜕皮甾酮组效果最佳.免疫组化染色发现,β-蜕皮甾酮组和仙灵骨葆组BMP-7、β-catenin表达阳性水平明显高于空白对照组,染色较深,但以β-蜕皮甾酮的密集度更高,染色更深.结论β-蜕皮甾酮可通过增强BMP-7、β-catenin表达促进BMSCs定向分化,发挥治疗骨质疏松性骨折的作用.Objective To explore the mechanism of β-ecdysterone in the teatment of osteoporotic fractures by regulating the expression of β-catenin/BMP and promoting the diferentiation of bone marrow stem clls.Methods Three month-old female TOPGAL mice were slected to establsh ovariectomized osteoporosis mouse models.Tibia fracture models were established in 3 months after ovariectomy.The mice were randomly divided into normal saline group.β-ecdysterone group and Xianling Gubao group.with 10 mice in each group.and the corresponding drugs were given intrgastric treatment on the second day after the fracture.After 4 weeks of continuous intragastric treatment,samples were taken for related index detection,and the serum estradiol content,tibia imaging,histopahologial changs,the expression levels of Bone morphogenetic protein-7BMP-7)andβ-catenin(β-catenin)in the callus of the mice in each group were compared.Results The test results of serum estradiol content showed that the serum estradiol content ofβ-ecdysterone group and Xianling Gubao group were 8.14±4.19 pg/mL and 12.23±4.92 pg/mL,respectively,which were signifcandly higher than normal saline group(3.27±3.40pg/mL)(all P<0.05).X-Tay test results showed that in the normal saline group,a small amount of sparse calus passed through and a small amount of extermal callus was formed at the fracture end,and the fracture line was visible,while theβ-ecdysterone group and the Xianling Gubao group had dense outer callus at the fracture end,and part of the medullary cavity was renewed.And the fracture line was blurred.Micro-CT scan results showed that the thickness of the cortical bone in the saline group was significantly thinner,and the bone trabecula was sparse,the thickness of the cortical bone in theβ-ecdysterone group and the Xianling Gubao group was sgnifianly better than that in the normal saline group.The structure of saller bones was relatively compact and uniform.HE staining found that the number and density of bone trabecula of the mice in theβ-ecdysterone group a

关 键 词：骨质疏松性骨折 β-蜕皮甾酮 骨形成蛋白-7 Β-连环蛋白 骨髓间充质干细胞 

分 类 号：R580[医药卫生—内分泌] R683[医药卫生—内科学]