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。
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.
作者
肖惟丹
熊政利
李俊
XIAO Weidan;XIONG Zhengli;LI Jun(Wuhan Orthopaedics Hospital of Integrated Traditional Chinese and Western Medicine,The Affiliated Hospital of Wuhan Sports University,Wuhan 430079,China;Department of Traditional Chinese Medicine,Wuhan Puren Hospital,Wuhan 430079,China)
出处
《陕西中医》
2025年第9期1172-1177,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家重点研发计划项目(2021YFC2501701)
武汉市医学科研项目(WZ21B02)。
