冬凌草甲素调节Hippo/YAP信号通路对骨质疏松大鼠成骨细胞凋亡的影响  

Effect of Oridonin on Apoptosis of Osteoblasts in Osteoporotic Rats by Regulating Hippo/YAP Signaling Pathway

作　　者：陆海峰 邹炳宏 朱亿 LU Haifeng;ZOU Binghong;ZHU Yi(Dazhou Orthopedic Hospital,Sichuan Dazhou 635000,China)

机构地区：[1]四川省达州骨科医院骨科,四川达州635000

出　　处：《河北医学》2024年第7期1100-1105,共6页Hebei Medicine

基　　金：四川省卫生健康委员会科研课题,(编号:19PJ035)。

摘　　要：目的:探讨冬凌草甲素(Ori)调节Hippo/Yes相关蛋白(YAP)信号通路对骨质疏松(OP)大鼠成骨细胞凋亡的影响。方法:随机选取10只大鼠为假手术组仅分离但不切除卵巢,其余大鼠通过切除双侧卵巢建立OP模型,将造模成功的大鼠随机分为OP组、不同剂量Ori(5mg/kg Ori、10mg/kg Ori、20mg/kg Ori)组、20mg/kg Ori+Hippo/YAP激活剂-Verteporfin(10mg/kg)组。干预后,收集腹主动脉血液,ELISA检测血清中骨钙素(BGP)、碱性磷酸酶(ALP)水平;分离股骨组织,双能X射线骨密度仪检测股骨矿含量、骨密度;HE检测股骨组织形态学变化;TUNEL检测成骨细胞凋亡变化;Western blot检测YAP、转录共激活因子PDZ结合基序(TAZ)蛋白表达。结果:假手术组大鼠股骨结构变化不明显,与假手术组相比,OP组股骨组织形态发生明显改变,BGP、ALP水平、股骨组织矿含量、骨密度、YAP、TAZ蛋白表达显著降低(P<0.05),成骨细胞凋亡率显著增加(P<0.05);与OP组相比,5mg/kg Ori组、10mg/kg Ori组、20mg/kg Ori组股骨组织形态得到改善,BGP、ALP水平、股骨组织矿含量、骨密度、YAP、TAZ蛋白表达显著增加(P<0.05),成骨细胞凋亡率显著降低(P<0.05),不同剂量Ori间具有统计差异(P<0.05);与20mg/kg Ori组相比,20mg/kg Ori+Verteporfin组股骨组织形态变化加重,BGP、ALP水平、股骨组织矿含量、骨密度、YAP、TAZ蛋白表达显著降低(P<0.05),成骨细胞凋亡率显著增加(P<0.05)。结论:Ori调节Hippo/YAP信号通路减少OP大鼠成骨细胞凋亡,减轻OP大鼠症状。Objective:To investigate the effect of oridonin(Ori)on osteoblast apoptosis in osteoporosis(OP)rats by regulating the Hippo/Yes-associated protein(YAP)signaling pathway.Methods:Ten rats were randomly selected as the sham surgery group,with only ovaries separated but not removed.The remaining rats were used to establish an OP model by removing both ovaries.The successfully modeled rats were randomly separated into the OP group,different doses of Ori(5 mg/kg Ori,10 mg/kg Ori,20 mg/kg Ori)groups,and 20 mg/kg Ori+Hippo/YAP activator-Vesteporfin(10 mg/kg)group.After the intervention,abdominal aortic blood was collected,and ELISA was applied to detect serum levels of osteocalcin(BGP)and alkaline phosphatase(ALP).The femoral tissue was separated,and a dual-energy X-ray bone density instrument was applied to detect femoral mineral content and bone density.HE was applied to detect morphological changes in femoral tissue.TUNEL was applied to detect changes in osteoblast apoptosis.Western blot was applied to detect the expression of YAP and transcription co-activator PDZ binding motif(TAZ)proteins.Results:There was no great change in the femoral structure of the rats in the sham surgery group.Compared with the sham surgery group,there was a great change in the morphology of the femoral tissue in the OP group,the levels of BGP and ALP,femoral tissue mineral content,bone density,YAP,and TAZ protein expression were greatly reduced(P<0.05),the apoptosis rate of osteoblasts was greatly increased(P<0.05).Compared with the OP group,the femoral tissue morphology was improved in the 5 mg/kg Ori group,10 mg/kg Ori group,and 20 mg/kg Ori group,the levels of BGP and ALP,femoral tissue mineral content,bone density,YAP,and TAZ protein expression were greatly increased(P<0.05),the apoptosis rate of osteoblasts was greatly decreased(P<0.05),there were statistical differences between different doses of Ori(P<0.05).Compared with the 20 mg/kg Ori group,the morphological changes of the femoral tissue in the 20 mg/kg Ori+Verteporfin group were

关 键 词：冬凌草甲素 Hippo/YAP信号通路 骨质疏松 成骨细胞 凋亡 

分 类 号：R285.5[医药卫生—中药学]