摘要
目的:探讨龙牙楤木皂苷Ⅳ对骨质疏松大鼠骨重建的影响及相关机制。方法:将大鼠随机分为假手术组、模型组、龙牙楤木皂苷Ⅳ低、中、高剂量组(25,50,100 mg·kg^(-1))及龙牙楤木皂苷Ⅳ+信号转导和转录激活因子3(STAT3)通路抑制组(100 mg·kg^(-1)+3.75 mg·kg^(-1)),每组8只。除假手术组外,其余各组大鼠构建骨质疏松大鼠模型。造模后第30天开始,龙牙楤木皂苷Ⅳ各剂量组灌胃给药,假手术组和模型组大鼠给与等体积生理盐水,1次/d,持续8周;STAT3通路抑制组大鼠在灌胃给与龙牙楤木皂苷Ⅳ的同时腹腔注射Stattic(其余组大鼠腹腔注射等量生理盐水),每2 d注射1次,持续8周。测定大鼠血清及骨组织中Runt相关转录子-2(Runx2)、骨形态发生蛋白2(BMP2)、碱性磷酸酶(AKP)、核因子κB受体活化因子配体(RANKL)水平,检测股骨骨密度(BMD),观察股骨组织病理变化,检测骨组织中细胞因子信号负调控因子3(SOCS3)、p-STAT3/STAT3蛋白水平。结果:与模型组相比,龙牙楤木皂苷Ⅳ低、中、高剂量组大鼠血清Runx2、BMP2、AKP水平,骨组织中Runx2、BMP2、AKP、p-STAT3/STAT3蛋白水平及股骨BMD值显著升高(P<0.05),血清RANKL水平及骨组织中RANKL、SOCS3蛋白水平显著降低(P<0.05),且呈剂量依赖性(P<0.05),股骨组织病理变化得到改善。与龙牙楤木皂苷Ⅳ中、高剂量组相比,龙牙楤木皂苷Ⅳ+STAT3通路抑制组大鼠以上各指标差异有统计学意义(P<0.05),股骨组织病理变化加重。结论:龙牙楤木皂苷Ⅳ可抑制SOCS3表达,激活STAT3通路,抑制骨吸收并促进骨形成,改善骨质疏松大鼠骨重建情况。
Objective:To investigate the effects and related mechanisms of Aralia elata saponinsⅣon bone remodeling in rats with osteoporosis.Methods:The rats were randomly divided into sham operation group,model group,Aralia elata saponinsⅣlow,medium and high dose groups(25,50,100 mg·kg^(-1))and Aralia elata saponinsⅣ+signal transduction and signal transducer and activator of transcription 3(STAT3)pathway inhibition group(100 mg·kg^(-1)+3.75 mg·kg^(-1))with 8 rats in each group.Except the sham operation group,the rats in the other groups were constructed osteoporotic rat model.On the 30 th day after modeling,Aralia elata saponinsⅣlow,medium and high dose groups were administered intragastrically,and rats in the sham operation group and model group were given equal volume of normal saline,once a day for 8 weeks;rats in the STAT3 pathway inhibition group were given Aralia elata saponinsⅣby intragastric administration and intraperitoneal injection of Stattic(the rats in the remaining groups were intraperitoneally injected with the same amount of normal saline)once every 2 days for 8 weeks.The levels of Runt-related transcript-2(Runx2),bone morphogenetic protein 2(BMP2),alkaline phosphatase(AKP)and nuclear factor kappa B receptor activator ligand(RANKL)in serum and bone tissue were detected,the bone mineral density was detected,the pathological changes of femur tissue were observed,the protein levels of suppressors of cytokine signaling 3(SOCS3)and p-STAT3/STAT3 in bone tissue were detected.Results:Compared with those in the model group,the levels of Runx2,BMP2 and AKP in serum,Runx2,BMP2,AKP and p-STAT3/STAT3 protein in bone tissue and BMD value of femur in the low,medium and high dose groups of Aralia elata saponinsⅣwere significant increased(P<0.05),serum RANKL level and bone tissue RANKL and SOCS3 protein levels were significantly reduced(P<0.05)in a dose-dependent manner(P<0.05);the pathological changes of femur tissue were improved.Compared with the Aralia elata saponinsⅣmedium and high dose groups,the above indicators in the Aralia elata saponinsⅣ+STAT3 pathway inhibition group had statistically significant differences(P<0.05),and the pathological changes in femoral tissue were aggravated.Conclusion:Aralia elata saponinⅣcan inhibit the expression of SOCS3,activate STAT3 pathway,inhibit bone resorption,promote bone formation and improve bone remodeling in osteoporotic rats.
作者
余昌明
刘奎
Yu Changming;Liu Kui(Department of Traumatic Orthopedics,Hubei 672 Orthopedics Hospital of Integrated Traditional Chinese and Western Medicine,Wuhan 430079,China)
出处
《中国药师》
CAS
2021年第11期1993-1997,共5页
China Pharmacist
