基于Nrf2通路探讨松脂醇二葡萄糖苷改善小鼠骨质疏松的机制研究

黄星翔, 钟超, 叶华, 徐春贻, 刘云飞, 蒋璐

中国临床解剖学杂志 ›› 2023, Vol. 41 ›› Issue (2) : 162-171.

PDF(6014 KB)
PDF(6014 KB)
中国临床解剖学杂志 ›› 2023, Vol. 41 ›› Issue (2) : 162-171. DOI: 10.13418/j.issn.1001-165x.2023.2.08
实验研究

基于Nrf2通路探讨松脂醇二葡萄糖苷改善小鼠骨质疏松的机制研究

  • 黄星翔1,    钟超2*,    叶华2,    徐春贻3,    刘云飞4,    蒋璐4
作者信息 +

Action mechanism of pinoresinol diglucoside on improving osteoporosis in mice based on Nrf2 pathway

  • Huang Xingxiang1, Zhong Chao2*, Ye Hua2, Xu Chunyi3, Liu Yunfei4, Jiang Lu4
Author information +
文章历史 +

摘要

目的    分析松脂醇二葡萄糖苷(Pinoresinol diglucoside,PD)改善骨质疏松的作用机制。  方法    微型CT分析小鼠小梁骨体积/总体积(bone volume/total volume,BV/TV)、平均小梁厚度(average trabecular thickness,Tb.Th)、平均小梁数目(average number of trabeculae,Tb.N)和平均小梁间距(average trabecular spacing,Tb.Sp);HE染色检测骨组织损伤;TRAP染色分析成骨细胞数量/骨周长(number of bone cells/bone circumference,N.Ob/B.Pm)、空泡率以及破骨细胞表面/骨表面百分比(osteoclast surface/bone surface,Ocs/BS);ELISA检测碱性磷酸酶(alkaline phosphatase,ALP)、抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)相对活性,超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Malondialdehyde,MDA)和谷胱甘肽(glutathione,GSH)含量;Wb检测核转录因子红细胞系2相关因子2(Nuclear factor erythroid-2-related factor 2,Nrf2)和HO-1表达。  结果   与假手术组相比,模型组小鼠骨丢失量增加,BV/TV、Tb.Th、Tb.N、N.Ob/B.Pm、ALP相对活性、SOD、GSH、Nrf2和HO-1表达水平明显下降,Tb.Sp、空泡率、Ocs/BS、TRAP相对活性和MDA水平明显上升(P<0.05);E2组和PD组小鼠与模型组小鼠变化趋势完全相反(P<0.05),PD组和E2组小鼠上述指标无显著差异(P>0.05)。  结论    PD可通过激活Nrf2信号通路改善小鼠骨质疏松症状。

Abstract

Objective    To analyze the action mechanism of pinoresinol diglucoside (PD) on improving osteoporosis.   Methods    The trabecular bone volume/total volume (BV/TV), average trabecular thickness (Tb.Th), average number of trabeculae (Tb.N) and average trabecular spacing (Tb.Sp) were analyzed by micro-CT. The damage of bone tissues was detected by HE staining. Number of bone cells/bone circumference (N.Ob/B.Pm), vacuole rate and osteoclast surface/bone surface (Ocs/BS) were analyzed by TRAP staining. The relative activities of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected by ELISA. The expressions of Nuclear factor erythroid-2-related factor 2 (Nrf2) and HO-1 were detected by Western Blotting.     Results    Compared with sham operation group, bone loss was increased in model group, BV/TV, Tb.Th, Tb.N, N.Ob/B.Pm, relative activity of ALP, SOD, GSH, Nrf2 and HO-1 expression levels were significantly decreased, Tb.Sp, vacuole rate, Ocs/BS, relative activity of TRAP and MDA level were significantly increased (P<0.05). The changes in E2 group and PD group were completely opposite to those in model group (P<0.05). There was no significant difference in the above indexes between PD group and E2 group (P>0.05).    Conclusions   PD can improve osteoporosis in mice by activating Nrf2 signaling pathway. 

关键词

松脂醇二葡萄糖苷;  /   / 骨质疏松;  /   / 核转录因子红细胞系2相关因子2;  /   / 成骨细胞;  /   / 破骨细胞;  /   / 氧化应激

Key words

Pinoresinol diglucoside;  /  Osteoporosis;  /  Nuclear factor erythroid-2-related factor 2 / Osteoblast;  /   / Osteoclast;  /   / Oxidative stress

引用本文

导出引用
黄星翔, 钟超, 叶华, 徐春贻, 刘云飞, 蒋璐. 基于Nrf2通路探讨松脂醇二葡萄糖苷改善小鼠骨质疏松的机制研究[J]. 中国临床解剖学杂志. 2023, 41(2): 162-171 https://doi.org/10.13418/j.issn.1001-165x.2023.2.08
Huang Xingxiang, Zhong Chao, Ye Hua, Xu Chunyi, Liu Yunfei, Jiang Lu. Action mechanism of pinoresinol diglucoside on improving osteoporosis in mice based on Nrf2 pathway[J]. Chinese Journal of Clinical Anatomy. 2023, 41(2): 162-171 https://doi.org/10.13418/j.issn.1001-165x.2023.2.08
中图分类号: R33    

参考文献

[1] Clynes MA, Harvey NC, Curtis EM, et al. The epidemiology of osteoporosis[J]. Br Med Bull, 2020, 133(1): 105-117. DOI: 10.1093/bmb/ldaa005.
[2]  Compston J. Reducing the treatment gap in osteoporosis[J]. Lancet Diabetes Endocrinol, 2020, 8(1): 7-9. DOI: 10.1016/S2213-8587(19)30378-X.
[3]  Johnston CB, Dagar M. Osteoporosis in older adults[J]. Med Clin North Am, 2020, 104(5): 873-884. DOI: 10.1016/j.mcna.2020.06.004.
[4]  Xin B, Mu S, Tan T, et al. Belief in and use of traditional Chinese medicine in Shanghai older adults: a cross-sectional study[J]. BMC Complement Med Ther, 2020, 20(1): 128-129. DOI: 10.1186/s12906-020-02910-x.
[5]  白璧辉, 谢兴文, 李鼎鹏, 等. 杜仲及其有效成分防治骨质疏松症研究进展[J]. 辽宁中医药大学学报, 2019, 21(1): 126-129. DOI: 10.13194/j.issn.1673-842x.2019.01.034.
[6]  赵永杰, 王翰宇, 胡广兵, 等. 中药辅助治疗原发性骨质疏松症的用药规律[J]. 西部中医药, 2018, 31(6): 65-68. DOI: 10.3969/j.issn.1004-6.
[7]  董航, 严娇, 谢铱子, 等. 杜仲治疗骨质疏松的网络药理学作用机制探讨[J]. 广州中医药大学学报, 2019, 36(9): 1413-1420. DOI: 10.13359/j.cnki.gzxbtcm.2019.09.023.
[8] Lei S, Wu S, Wang G, et al. Pinoresinol diglucoside attenuates neuroinflammation, apoptosis and oxidative stress in a mice model with Alzheimer's disease[J]. Neuroreport, 2021, 32(3): 259-267. DOI: 10.1097/WNR.0000000000001583.
[9] Deeks ED. Denosumab: a review in postmenopausal osteoporosis[J]. Drugs Aging, 2018, 35(2): 163-173. DOI: 10.1007/s40266-018-0525-7.
[10]Agidigbi TS, Kim C. Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases[J]. Int J Mol Sci, 2019, 20(14): 3576. DOI: 10.3390/ijms20143576.
[11]Geng Q, Gao H, Yang R, et al. Pyrroloquinoline quinone prevents estrogen deficiency-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence[J]. Int J Biol Sci, 2019, 15(1): 58-68. DOI: 10.7150/ijbs.25783.
[12]叶胜, 曹钰. Nrf2-HO1信号通路调控脑缺血-再灌注氧化应激损伤的研究进展[J]. 中华急诊医学杂志, 2019, 28(12): 1571-1575. DOI: 10.3760/cma.j.issn.1671-0282.2019.12.026.
[13]Sun GH, Liao Y, Liao Y, et al. [Electroacupuncture intervention improves cartilage degeneration and subchondral bone osteoporosis of knee-joint possibly by adjusting opg/rank/rankl signaling in ovariectomized rats][J]. Zhen Ci Yan Jiu, 2018, 43(12): 781-7. DOI: 10.13702/j.1000-0607.170591.
[14]Song C, Yang X, Lei Y, et al. Evaluation of efficacy on RANKL induced osteoclast from RAW264.7 cells[J]. J Cell Physiol, 2019, 234(7): 11969-11975. DOI: 10.1002/jcp.27852.
[15]Ding LZ, Teng X, Zhang ZB, et al. Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells[J]. Int J Mol Med, 2018, 41(5): 2517-2526. DOI: 10.3892/ijmm.2018.3506.
[16]高晓波, 徐红丹, 祁永华, 等. 松脂醇二葡萄糖苷对人皮肤成纤维细胞胶原蛋白分泌机制的研究[J]. 国际中医中药杂志. 2017, 39(2): 131-135. DOI: 10.3760/cma.j.issn.1673-4246.2017.02.010.
[17]Zhao B. Does TNF promote or restrain osteoclastogenesis and inflammatory bone resorption[J]? Crit Rev Immunol, 2018, 38(4): 253-261. DOI: 10.1615/CritRevImmunol.2018025874.

[18]吴钰坤, 韩杰, 温帅波. 骨折愈合过程中Runx2基因的作用机制[J]. 中国组织工程研究, 2021, 25(14): 2274-2279. DOI: 10.3969/j/issn.2095-4344.3111.

[19]Sleeman A, Clements JN. Abaloparatide: a new pharmacological option for osteoporosis[J]. Am J Health Syst Pharm, 2019, 76(3): 130-135. DOI: 10.1093/ajhp/zxy022.
[20]朱静栋, 孔西建, 黄付伟, 等. 骨松强骨方对去卵巢大鼠股骨骨密度、骨强度和骨结构的影响[J]. 中国中医骨伤科杂志, 2017, 25(11): 5-10.
[21]张向阳, 梁朝革, 唐献忠, 等. 骨质疏松患者股骨头不同区域骨结构与生物力学分析[J]. 医用生物力学, 2017, 32(1): 77-82. DOI:10.16156/j.1004-7220.2017.01.013.
[22]Zhu S, Zhu J, Zhen G, et al. Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain[J]. J Clin Invest. 2019, 129(3): 1076-1093. DOI: 10.1172/JCI121561.
[23]Kim JH, Kim M, Jung HS, et al. Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation[J]. Int J Mol Med, 2019, 44(3): 913-926. DOI: 10.3892/ijmm.2019.4269.
[24]万烨东, 陈泽维, 王枫, 等. 佛手苷内酯对磷酸三钙磨损颗粒所致假体周围骨溶解的影响[J]. 中国运动医学杂志, 2020, 39(3): 219-225. DOI: 10.3969/j.issn.1000-6710.2020.03.007.
[25]刘扬捷, 龚晓健, 王永庆. 成骨细胞的功能与损伤和骨质疏松的防治[J]. 药学与临床研究, 2019, 27(3): 201-205. DOI: 10.13664/j.cnki.pcr.2019.03.011.
[26]程韶, 舒冰, 赵永见, 等. 氧化应激对骨重建的影响[J]. 中国骨质疏松杂志,2019, 25(10): 1478-1482. DOI: 10.3969/j.issn.1006-7108. 2019. 10.024.
[27]李蕊, 李琳, 田怿淼, 等. 八子补肾胶囊对衰老小鼠骨质量的保护作用及其对SIRT6/NF-κB/cathepsin K通路的影响[J]. 中国骨质疏松杂志,2021, 27(3): 313-318, 328. DOI: 10.3969/j.issn.1006-7108. 2021.0 3.001.
[28]罗毅玲, 周丕琪, 王刚. 温针灸联合古方青娥丸加味对绝经后骨质疏松腰腿痛患者疼痛、氧化应激及性激素水平的影响[J]. 湖南中医药大学学报,2019, 39(8): 977-981. DOI: 10.3969/j.issn.1674-070X. 2019. 08.011.
[29]Cheng J, Wang H, Zhang Z, et al. Stilbene glycoside protects osteoblasts against oxidative damage via Nrf2/HO-1 and NF-κB signaling pathways[J]. Arch Med Sci, 2019, 15(1): 196-203. DOI: 10.5114/aoms.2018.79937.
[30]陈婷婷, 黄天一, 李梦雨, 等. 1,2,3,4,6-五没食子酰葡萄糖的骨保护作用与Nrf2/HO-1信号通路的相关性研究[J]. 药学学报, 2020, 55(5): 153-160. DOI: 10.16438/j.0513-4870.2019-0773.

基金

四川省卫计委科研课题(16PJ433);成都市科技局科研课题(2021-YF05-00742-SN)

PDF(6014 KB)

Accesses

Citation

Detail

段落导航
相关文章

/