积雪草苷调节RANKL/RANK/OPG信号通路对类风湿关节炎大鼠骨代谢和骨密度的影响OA
Effects of Asiaticoside on bone metabolism and bone density in rheumatoid arthritis rats by regulating RANKL/RANK/OPG signaling pathway
目的:探讨积雪草苷(ASI)对类风湿关节炎(RA)大鼠骨代谢和骨密度及核因子-κB受体活化因子配体(RANKL)-核因子-κB受体活化因子(RANK)-骨保护素(OPG)信号通路的影响.方法:构建RA模型大鼠并随机分为模型组(Model组),ASI低、高剂量组(ASI-L、ASI-H组),OPG组,ASI高剂量+OPG组(ASI-H+OPG组),每组12只.另取12只健康大鼠作为对照组(Control组).分别对大鼠进行骨密度分析,Micro-CT检测骨微结构,ELISA检测血清骨代谢指标Runx2、OC、ALP、CTX水平、炎症因子指标IL-1β、TNF-α和IL-6水平,HE染色观察关节组织病变,Western blot检测RANKL、RANK、OPG蛋白表达.结果:与Control组相比,Model组大鼠软骨组织病理损伤严重、炎症细胞大面积浸润,破骨细胞数量增多,骨密度(BMD)和骨代谢指标Runx2、OC及Tb.Th、Tb.N、BV/TV和Conn.D指标显著降低,Tb.Sp、SMI、ALP、CTX和炎症因子水平IL-1β、TNF-α和IL-6显著升高,RANKL、RANK蛋白表达显著升高,OPG蛋白表达显著下降(P<0.05);与Model组相比,随着ASI剂量增加,ASI-L、ASI-H组大鼠软骨组织病理损伤减轻、炎症细胞浸润减少,破骨细胞数量减少,BMD和骨代谢指标Runx2、OC水平及Tb.Th、Tb.N、BV/TV和Conn.D指标显著升高,Tb.Sp、SMI、ALP、CTX和炎症因子IL-1β、TNF-α和IL-6水平显著降低,RANKL、RANK蛋白表达明显降低,OPG蛋白表达显著升高(P<0.05);与ASI-H组相比,ASI-H+OPG组大鼠软骨组织病理损伤及炎症得到更好改善,破骨细胞数量减少,BMD和骨代谢水平更接近Control组,RANKL、RANK蛋白表达显著降低,OPG蛋白表达显著升高(P<0.05).结论:ASI可改善大鼠骨密度和骨代谢,降低炎症反应,改善关节组织病理损伤,其潜在机制可能与调控RANKL/RANK/OPG信号通路有关.
Objective:To investigate effects of Asiaticoside(ASI)on bone metabolism,bone density and receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)/osteoprotegerin(OPG)signaling pathway in rheu-matoid arthritis(RA)rats.Methods:A RA rat model was constructed and randomly grouped into Model group,low and high doses ASI groups(ASI-L,ASI-H groups),OPG group and high-dose ASI+OPG group(ASI-H+OPG group),with 12 rats in each group.Another 12 healthy rats were included as control group.All rats were subjected to bone density analysis.Micro CT was used to detect bone microstructure.ELISA was applied to detect serum bone metabolism indicators Runx2,OC,ALP,CTX and inflammatory factor indicators IL-1β,TNF-α and IL-6 levels.Joint tissue lesions were observed by HE staining.Western blot was applied to detect expres-sions of RANKL,RANK and OPG proteins.Results:Compared with Control group,Model group showed severe cartilage tissue dam-age,extensive infiltration of inflammatory cells,number of osteoclasts was increased,bone mineral density(BMD)and bone metabo-lism indicators Runx2,OC levels,Tb.Th,Tb.N,BV/TV and Conn.D indexes were obviously decreased,levels of Tb.SP,SMI,ALP,CTX,and inflammatory factors IL-1β,TNF-α and IL-6 were obviously increased,expressions of RANKL and RANK proteins were obviously increased,expression of OPG protein was prominently decreased(P<0.05).Compared with Model group,with increase of ASI dose,degree of cartilage tissue damage,inflammatory cell infiltration,number of osteoclasts reduced in ASI-L and ASI-H groups,BMD and bone metabolism indicators Runx2,OC levels,Tb.Th,Tb.N,BV/TV,Conn.D indexes were prominently increased,while levels of Tb.SP,SMI,ALP,CTX,inflammatory factors IL-1β,TNF-α and IL-6 were obviously decreased,expres-sions of RANKL and RANK proteins were obviously decreased,and expression of OPG protein was prominently increased(P<0.05).Compared with ASI-H group,ASI-H+OPG group showed better improvement in cartilage tissue damage and inflammatory symptoms,number of osteoclasts decreased,BMD and bone metabolism levels were closer to Control group,expressions of RANKL and RANK proteins were prominently reduced,while expression of OPG protein was obviously increased(P<0.05).Conclusion:ASI can improve bone density and metabolism,reduce inflammatory response,and improve joint tissue damage in rats,whose potential mechanism may be related to regulation of RANKL/RANK/OPG signaling pathway.
张航;熊成欢;唐芳
贵州中医药大学第二附属医院检验科,贵阳 550003贵州中医药大学第二附属医院药剂科,贵阳 550003贵州中医药大学第二附属医院风湿免疫科,贵阳 550003
医药卫生
积雪草苷类风湿关节炎骨密度骨代谢RANKL/RANK/OPG通路
AsiaticosideRheumatoid arthritisBone densityBone metabolismRANKL/RANK/OPG pathway
《中国免疫学杂志》 2026 (1)
35-40,6
国家自然科学基金项目(82160917).
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