骨碎补总黄酮抑制Notch1/Hes1/Prdx1通路对骨质疏松大鼠抗氧化能力的影响
The effect of total flavonoids from Rhizoma Drynariae on antioxidant capacity in osteoporosis rats by the inhibition of Notch1/Hes1/Prdx1 pathway
  
DOI:10.3969/j.issn.1006-7108.2023.10.006
中文关键词:  骨碎补总黄酮  绝经后骨质疏松症  抗氧化  Notch信号通路
英文关键词:total flavonoids of rhizoma drynariae  postmenopausal osteoporosis  antioxidant  Notch signaling pathway
基金项目:湖北省武汉市卫生健康委员会科研计划资助项目(WZ20Q09);湖北省自然科学基金创新发展联合基金项目(2022CFD150); 湖北省中医药管理局中医药科研项目(ZY2023F009)
作者单位
鲁林1 方虹2* 1. 武汉市中医医院湖北 武汉 430000 2. 湖北省中医院湖北 武汉 430000 
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中文摘要:
      目的 探讨骨碎补总黄酮(total flavonoids of rhizoma drynariae, TFRD)对去卵巢(ovariectomized, OVX)骨质疏松大鼠氧化应激的影响及其机制。方法 构建OVX骨质疏松大鼠模型,分别用TFRD和补佳乐(BJL)灌胃,给药12周后称重,取股骨组织和血清。HE染色观察股骨组织形态学变化,免疫组织化学染色检测股骨组织中骨保护素(osteoprotegerin,OPG)和骨形态发生蛋白2(bone morphogenetic protein 2,BMP-2)的表达,生化试剂盒检测血清中超氧化物歧化酶(superoxide dismutase, SOD)、丙二醛(malondialdehyde,MDA)和活性氧(reactive oxygen species,ROS)的水平,Western blot检测股骨组织中Notch1、发状分裂相关增强子1(hairy and enhancer of split 1,Hes1)、过氧化还原酶1(peroxiredoxin 1,Prdx1)蛋白的表达。结果 TFRD和BJL均能显著抑制OVX所致的大鼠体重的增加(P<0.01),并改善骨小梁的结构的完整性,缩短骨小梁间距,显著降低病理评分(P<0.01)。此外,TFRD和BJL均能升高血清SOD水平(P<0.01),降低MDA和ROS水平(P<0.01),促进股骨组织中OPG、BMP-2的表达(P<0.01),并抑制Notch1、Hes1和Prdx1蛋白的表达(P<0.01)。结论 TFRD可抑制OVX大鼠的氧化应激反应,调控骨稳态,其发挥抗骨质疏松的作用可能与抑制Notch1/Hes1/Prdx1通路有关。
英文摘要:
      Objective To investigate the effect of total flavonoids of rhizoma drynariae (TFRD) on oxidative stress and its mechanism in ovariectomized (OVX) osteoporosis rats. Methods OVX rat model of osteoporosis was established. TFRD and BJL were administered by gavage, respectively. After 12 weeks of administration, femur tissue and serum were taken from the rats. The histopathological changes of femurwas observed by HE staining, the expressions of osteoprotegerin (OPG) and bone morphogenetic protein 2 (BMP-2) in femur tissue were detect by immunohistochemical staining,the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) in serum were measured by biochemical kit,and the expression of Notch1, hairy and enhancer of split 1 (Hes1) and peroxiredoxin 1 (Prdx1) were detected by Western blot. Results Both TFRD and BJL could significantly inhibit OVX-induced weight gain (P<0.01), improve the structural integrity of trabecular bone and shorten the trabecular spacing, and significantly reduced the pathological score (P<0.01). In addition, both TFRD and BJL can increase serum SOD levels (P<0.01), decrease MDA and ROS levels (P<0.01), promote the expression of OPG and BMP-2 in femur tissue (P<0.01), and inhibit the expression of Notch1, Hes1 and Prdx1 proteins (P<0.01). Conclusion TFRD can inhibit oxidative stress response and regulate bone homeostasis in OVX rats, and its anti-osteoporosis effect may be related to the inhibition of Notch1/Hes1/Prdx1 pathway.
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