[1]肖惟丹,熊政利,李俊.巴戟天调控Notch1/Hes1/Prdx1通路对绝经后骨质疏松大鼠骨质量、生物力学及股骨组织形态的影响[J].陕西中医,2025,46(9):1172-1177.[doi:DOI:10.3969/j.issn.1000-7369.2025.09.004]
 XIAO Weidan,XIONG Zhengli,LI Jun.Effects of Morbidin on Notch1/Hes1/Prdx1 pathway on bone mass,biomechanics and femur morphology in postmenopausal osteoporosis rats[J].,2025,46(9):1172-1177.[doi:DOI:10.3969/j.issn.1000-7369.2025.09.004]
点击复制

巴戟天调控Notch1/Hes1/Prdx1通路对绝经后骨质疏松大鼠骨质量、生物力学及股骨组织形态的影响

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年9期
页码:
1172-1177
栏目:
基础研究
出版日期:
2025-09-05

文章信息/Info

Title:
Effects of Morbidin on Notch1/Hes1/Prdx1 pathway on bone mass,biomechanics and femur morphology in postmenopausal osteoporosis rats
作者:
肖惟丹1熊政利1李俊2
(1.武汉中西医结合骨科医院 武汉体育学院附属医院,湖北 武汉 430079;2.武汉市普仁医院中医科,湖北 武汉 430079)
Author(s):
XIAO Weidan1XIONG Zhengli1 LI Jun2
(1.Wuhan Orthopaedics Hospital of Integrated Traditional Chinese and Western Medicine,The Affiliated Hospital of Wuhan Sports University,Wuhan 430079,China;2.Department of Traditional Chinese Medicine,Wuhan Puren Hospital,Wuhan 430079,China)
关键词:
巴戟天发状分裂相关增强子1过氧化还原酶1骨质疏松骨质量生物力学骨代谢
Keywords:
Morinda officinalisHes1Prdx1OsteoporosisBone qualityBiomechanicsBone metabolism
分类号:
R 271.116
DOI:
DOI:10.3969/j.issn.1000-7369.2025.09.004
文献标志码:
A
摘要:
目的:探究巴戟天调控Notch1/发状分裂相关增强子1/过氧化还原酶1(Notch1/Hes1/Prdx1)通路对绝经后骨质疏松(PMOP)大鼠骨质量、生物力学及股骨组织形态的影响。方法:将大鼠随机分为假手术组、模型组、巴戟天组、抑制剂组、联合组五组(各10只),除假手术组外均以双卵巢切除的方法建立PMOP大鼠模型。巴戟天组以18 g/kg巴戟天多糖灌胃,抑制剂组尾静脉注射1 mg/kg DAPT(Notch1抑制剂),联合组采用18 g/kg巴戟天多糖灌胃+1 mg/kg DAPT尾静脉注射,假手术组、模型组不予干预,1次/d,各组持续干预30 d。双能X线骨密度仪测量大鼠股骨、胫骨标本骨密度(BMD),生物力学试验机检测股骨弹性模量、最大载荷、屈服强度、断裂点载荷,全自动化学发光测定仪检测尿液、血液中的尿羟脯氨酸(HOP)、尿脱氧吡啶诺啉(DPD)、血浆抗酒石酸酸性磷酸酶(TRACP)水平,HE染色观察股骨组织形态,免疫印迹检测骨组织中Notch1、Hes1、Prdx1蛋白水平。结果:干预30 d后,与假手术组比较,模型组、巴戟天组、抑制剂组、联合组股骨、胫骨BMD值、弹性模量、最大载荷、屈服强度、断裂点载荷降低,HOP、DPD、TRACP、Notch1、Hes1、Prdx1蛋白水平升高(P<0.05)。与模型组比较,巴戟天组、抑制剂组、联合组股骨、胫骨BMD值、弹性模量、最大载荷、屈服强度、断裂点载荷升高,联合组最高,HOP、DPD、TRACP、Notch1、Hes1、Prdx1降低,联合组最低(P<0.05)。巴戟天组、抑制剂组比较无统计学差异(P>0.05)。与模型组比较,巴戟天组、抑制剂组、联合组股骨组织形态明显改善,联合组形态最佳。结论:巴戟天可抑制PMOP大鼠骨量流失,改善骨组织生物力学及组织形态,抑制骨代谢因子HOP、DPD、TRACP表达,其作用机制可能是抑制Notch1/Hes1/Prdx1信号通路。
Abstract:
Objective:To investigate the effects of Morinda officinalis on bone quality,biomechanics,and femoral histomorphology in postmenopausal osteoporosis (PMOP) rats by regulating the Notch1/Hes1/Prdx1 pathway.Methods:Rats were randomly divided into five groups (n=10 each):sham-operated group,model group,Morinda officinalis group,inhibitor group,and combination group.PMOP rat models were established by bilateral ovariectomy in all groups except the sham-operated group.The Morinda officinalis group received 18 g/kg of Morinda officinalis polysaccharide via oral gavage,the inhibitor group received 1 mg/kg DAPT (a Notch1 inhibitor) via tail vein injection,and the combination group received both 18 g/kg Morinda officinalis polysaccharide orally and 1 mg/kg DAPT via tail vein injection.The sham-operated and model groups received no intervention.All interventions were administered once daily for 30 days.Bone mineral density (BMD) of the femur and tibia was measured using dual-energy X-ray absorptiometry.Biomechanical properties,including elastic modulus,maximum load,yield strength,and fracture load,were assessed using a biomechanical testing machine.Levels of urinary hydroxyproline (HOP),urinary deoxypyridinoline (DPD),and plasma tartrate-resistant acid phosphatase (TRACP) were measured using an automated chemiluminescence analyzer.Femoral histomorphology was observed using HE staining,and protein levels of Notch1,Hes1,and Prdx1 in bone tissue were detected by Western blot.Results:After 30 days of intervention,compared with the sham-operated group,the model group,Morinda officinalis group,inhibitor group,and combination group showed decreased BMD values of the femur and tibia,reduced elastic modulus,maximum load,yield strength,and fracture load,and increased levels of HOP,DPD,TRACP,Notch1,Hes1,and Prdx1 proteins (P<0.05).Compared with the model group,the Morinda officinalis group,inhibitor group,and combination group exhibited increased BMD values,elastic modulus,maximum load,yield strength,and fracture load,with the combination group showing the highest values.Levels of HOP,DPD,TRACP,Notch1,Hes1,and Prdx1 were decreased,with the combination group showing the lowest levels (P<0.05).There was no significant difference between the Morinda officinalis group and the inhibitor group (P>0.05).Compared with the model group,the Morinda officinalis group,inhibitor group,and combination group showed significant improvement in femoral histomorphology,with the combination group exhibiting the best morphology.Conclusion:Morinda officinalis can inhibit bone loss,improve bone biomechanics and histomorphology,and suppress the expression of bone metabolism factors HOP,DPD,and TRACP in PMOP rats.The underlying mechanism may involve the inhibition of the Notch1/Hes1/Prdx1 signaling pathway.

参考文献/References:

[1]MOHEBBI R,SHOJAA M,KOHL M,et al.Exercise training and bone mineral density in postmenopausal women:An updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators[J].Osteoporos Int,2023,34(7):1145-1178.
[2]AYERS C,KANSAGARA D,LAZUR B,et al.Effectiveness and safety of treatments to prevent fractures in people with low bone mass or primary osteoporosis:A living systematic review and network meta-analysis for the American college of physicians[J].Ann Intern Med,2023,176(2):182-195.
[3]DU Y,ZHENG Q,OU Z H,et al.Efficacy and safety of Morinda officinalis oligosaccharide capsules for depressive disorder:A systematic review and meta-analysis[J].Braz J Psychiatry,2021,43(3):306-313.
[4]黄清霞,覃川娴,何泽源,等.巴戟天化学成分、药理作用及质量标志物预测分析[J].中华中医药学刊,2022,40(7):251-258.
[5]鲁林,方虹.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[J].中国骨质疏松杂志,2023,29(10):1431-1436.
[6]白洁,张全华,白孟海.大鼠骨质疏松模型的建立与鉴定[J].成都医学院学报,2012,7(4):586-587.
[7]白如君,邢晓磊,张虎.巴戟天多糖对骨质疏松大鼠骨质量、生物力学、β2肾上腺素能受体及OX-LDL水平的影响[J].中国老年学杂志,2023,43(13):3251-3255.
[8]沈灵杰,秦超,刘合飞.自体富血小板血浆通过Notch1调节骨质疏松大鼠骨折愈合[J].中国骨质疏松杂志,2024,30(2):181-186.
[9]KVERKA M,STEPAN J J.Associations among estrogens,the gut microbiome and osteoporosis[J].Curr Osteoporos Rep,2024,23(1):2.
[10]马远征,王以朋,刘强,等.中国老年骨质疏松诊疗指南(2018)[J].中国老年学杂志,2019,39(11):2557-2575.
[11]周妍妍,周晓洁,闫博文,等.巴戟天化学成分及药理作用研究进展[J].辽宁中医药大学学报,2021,23(10):1-5.
[12]毕俊华,杨燕,颛洪娟,等.基于分子对接技术探讨巴戟天改善子宫内膜容受性的机制[J].中国性科学,2024,33(8):126-131.
[13]沈燚,孙艺琦,李鹤鸣,等.巴戟天环烯醚萜苷下调GSK-3β抑制JAK2/STAT3和NF-κB通路减轻Ⅱ型胶原诱导的关节炎大鼠骨破坏的机制[J].药学学报,2024,59(10):2763-2772.
[14]WANG Y,HAN X,SHI J,et al.Distinct metabolites in osteopenia and osteoporosis:A systematic review and meta-analysis[J].Nutrients,2023,15(23):4895.
[15]孙鹏,张国华,陈超斌,等.血清Irisin、SOST、H2S与膝骨关节炎合并骨质疏松症患者骨密度、骨代谢标志物的相关性及其预测价值[J].现代生物医学进展,2024,24(10):1980-1984.
[16]朱超,茹平,罗文强.骨质疏松性椎体压缩性骨折患者血清N-MID和尿液DPD水平与椎体愈合程度的相关性研究[J].现代检验医学杂志,2020,35(4):130-133.
[17]LU L,WANG Z,ZHANG H,et al.Drynaria fortunei improves lipid profiles of elderly patients with postmenopausal osteoporosis via regulation of Notch1-NLRP3 inflammasome-mediated inflammation[J].Gynecol Endocrinol,2022,38(2):176-180.
[18]鲁林,方虹.基于Notch1-Hes1-Prdx蛋白家族通路探究强骨胶囊治疗绝经后骨质疏松的炎症及氧化应激机制[J].中国医药导报,2023,20(23):8-15.
[19]QU R,PENG Y,XU S,et al.RBPJ knockdown promotes M2 macrophage polarization through mitochondrial ROS-mediated Notch1-Jagged1-Hes1 signaling pathway in uveitis[J].Inflammation,2025,48(1):133-150.
[20]VIECELI D S F,AQUILA G,FORTINI F,et al.Context dependent function of ROS in the vascular endothelium:The role of the Notch pathway and shear stress[J].Biofactors,2017,43(4):475-485.
[21]刘茜.巴戟天糖链对血管新生中Notch信号通路的作用研究[D].郑州:郑州大学,2012.
[22]李静,尉娜,刘亚美,等.γ-分泌酶抑制剂DAPT阻断Notch通路并纠正脑卒中后抑郁大鼠Th17/Treg失衡[J].中国病理生理杂志,2021,37(3):393-399.
[23]刘美霞,刘剑刚,李浩.以γ分泌酶为靶点治疗阿尔茨海默病的中药单体及组分研究进展[J].中国中西医结合杂志,2014,34(3):376-379.
[24]AHMED W,LINGNER J.PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerase[J].Genes & Development,2018,32(9-10):658-669.
[25]姜涛,徐卫凡,蒋益萍,等.巴戟天丸组方对Aβ损伤成骨细胞的作用及基于网络药理学的机制研究[J].药学实践与服务,2024,42(7):285-290.

相似文献/References:

[1]袁佳莹,佟智颖,赵家义,等.巴戟天临床应用研究进展[J].陕西中医,2022,(6):807.[doi:DOI:10.3969/j.issn.1000-7369.2022.06.032]
 YUAN Jiaying,TONG Zhiying,ZHAO Jiayi,et al.Clinical application progress on morinda officinalis[J].,2022,(9):807.[doi:DOI:10.3969/j.issn.1000-7369.2022.06.032]

备注/Memo

备注/Memo:
国家重点研发计划项目(2021YFC2501701);武汉市医学科研项目(WZ21B02)
更新日期/Last Update: 2025-09-08