金刚丸调节Hippo信号通路mRNA表达防治OVX大鼠骨质疏松作用机制
Effect of Jingang Pill on preventing and treating osteoporosis in OVX rats by regulating the expression of Hippo signal pathway core gene mRNA
  
DOI:10.3969/j.issn.1006-7108.2022.08.016
中文关键词:  绝经后骨质疏松症  金刚丸  补肾填精法  Hippo信号通路
英文关键词:postmenopausal osteoporosis  Jingang Pill  reinforcing kidney to replenish essence method  hippo signal pathway
基金项目:基金项目:2020年辽宁省教育厅科学研究经费项目 (L202001)
作者单位
王剑1 李屹1 王实1 刘永林1 刘秀1 丰雪妮1 马越娇1 郭婧潭1 刘剑辉1 刘文艳1 张景云1 马金1 宋光熠1 郑洪新2* 1.辽宁医药职业学院辽宁 沈阳 110101 2.辽宁中医药大学辽宁 沈阳 110847 
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中文摘要:
      摘要:目的 基于Hippo信号通路核心基因mRNA表达,探索具有补肾填精壮骨之效的金刚丸治疗去卵巢(ovariectomized,OVX)大鼠骨质疏松症的疗效机制。方法 通过OVX法建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分正常组、假手术组、模型组、金刚丸高剂量组、金刚丸中剂量组、金刚丸低剂量组、仙灵骨葆对照组、骨化三醇对照组。灌胃12周后,通过X射线骨密度仪检测骨密度、镜下观察股骨头显微形态结构、ELISA法检测血清ALP、实时定量RT-PCR检测骨组织Mst2、Lats1、Taz mRNA表达。结果 ①与正常组比较,模型组股骨骨密度显著降低(P<0.01)、骨微结构显著破坏、血清ALP显著降低(P<0.01)、骨组织Mst2、Lats1 mRNA表达显著升高(P<0.01)、Taz mRNA表达显著降低(P<0.01);②与模型组比较,除金刚丸低剂量组外,各给药组的骨密度均显著升高(P<0.01),各给药组骨微结构破坏均得到改善、血清ALP均显著升高(P<0.01)、骨组织Mst2、Lats1 mRNA表达均显著降低(P<0.01)、Taz mRNA表达均显著升高(P<0.01),均以金刚丸高剂量组最为显著。结论 骨组织Hippo信号通路核心基因Mst2、Lats1 mRNA表达上调,Taz mRNA表达下调可能是PMOP的发病机制之一;金刚丸可能通过下调骨组织Hippo信号通路核心基因Mst2、Lats1 mRNA表达、上调Taz mRNA表达的机制,有效防治PMOP。
英文摘要:
      Abstract: Objective To explore the therapeutic mechanism of Jingang Pill with the function of reinforcing kidney essence to strengthen bone on ovariectomized(OVX) rat osteoporosis based on mRNA expression of Hippo signal pathway core genes. Methods Postmenopausal Osteoporosis(PMOP) rat model was established with ovariectomy. All the rats were divided into 8 groups: normal group, sham-operated group, model group, Jingang Pill high-dose group,Jingang Pill middle-dose group, Jingang Pill low-dose group, Xianlinggubao control group and calcitriol control group.After 12 weeks of drug administration,bone mineral density(BMD) was detected using X-ray bone density apparatus,microstructure of femoral head was observed with microscope, serum ALP was detected using ELISA and mRNA expression of Mst2,Lats1,Taz in bone was detected using real-time quantitative RT-PCR. Results ①Compared to those in normal group,bone microstructure in model group damaged significantly, femur BMD, serum ALP, mRNA expression of Taz in bone in model group decreased significantly (P<0.01), and mRNA expression of Mst2, Lats1 in bone in model group increased significantly(P<0.01).②Compared to those in model group, the damage of bone microstructure improved in all treatment groups, BMD increased significantly(P<0.01) in all treatment groups except Jingang Pill low-dose group,serum ALP,mRNA expression of Taz in bone increased significantly(P<0.01) in all treatment groups,and mRNA expression of Mst2, Lats1 in bone decreased significantly(P<0.01) in all treatment groups.The most significant difference was found in Jingang Pill high-dose group. Conclusion The mRNA expression of mst2 and LATS1, the core genes of Hippo signaling pathway, is up-regulated in bone tissue, and the down-regulation of TAZ mRNA may be one of the pathogenesis of PMOP; Jingang pill may effectively prevent and treat PMOP by down regulating the expression of core genes mst2 and LATS1 mRNA of Hippo signal pathway in bone tissue and up regulating the expression of TAZ mRNA.
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