摘要
目的基于高迁移率族蛋白1(HMGB1)/晚期糖基化终产物受体(RAGE)/核因子-κB(NF-κB)信号通路,探讨右归丸(You Gui Wan,YGW)对膝骨关节炎(knee osteoarthritis,KOA)大鼠模型关节软骨组织的保护机制。方法改良Hulth法制备KOA大鼠模型。将60只SPF级SD大鼠随机分为假手术(SHAM)组、模型(KOA)组、右归丸低剂量(KOA+YGWL)组、中剂量(KOA+YGWM)组、高剂量(KOA+YGWH)组、硫酸氨基葡萄糖阳性对照(KOA+GS)组。造模6周后给予相应药物灌胃干预,灌胃8周后取材,番红O固绿染色观察关节软骨组织病理改变,进行关节损伤国际骨关节炎研究协会(OARSI)评分,ELISA检测炎症因子含量变化,RT-PCR和Western blot检测HMGB1、RAGE、NF-κB基因和蛋白表达变化。结果KOA+YGWM组、KOA+YGWH组和KOA+GS组关节软骨损伤程度、OARSI评分、血清PGE2含量和膝关节软骨组织RAGE、NF-κB蛋白表达明显低于KOA组,KOA+YGWL组、KOA+YGWM组、KOA+YGWH组和KOA+GS组大鼠血清IL-18、COX2含量和关节软骨组织中HMGB1、RAGE、NF-κB基因表达及HMGB1蛋白表达也明显低于KOA组(P<0.05或P<0.01)。KOA+YGWL组大鼠OARSI评分、血清PGE2含量和关节软骨组织中HMGB1基因表达及NF-κB、HMGB1蛋白表达显著高于KOA+GS组,KOA+YGWL组、KOA+YGWM组大鼠膝关节软骨组织中RAGE、NF-κB基因表达和RAGE蛋白表达也明显高于KOA+GS组,而KOA+YGWH组大鼠膝关节软骨组织中RAGE、NF-κB基因表达明显低于KOA+GS组(P<0.01)。结论右归丸能够减轻膝骨关节炎模型关节软骨组织损伤,其机制与抑制HBGB1/RAGE/NF-κB信号通路下游的炎症因子分泌,进而抑制炎症反应密切相关。
Objective Exploring the molecular mechanism of You Gui Wan(YGW)in inhibiting the inflammatory response of articular cartilage tissue in knee osteoarthritis(KOA)model based on high mobility group box1(HMGB1)/advanced glycation end product receptor(RAGE)/nuclear factor-κB(NF-κB)signaling pathway.Methods Sixty Sprague-Dawley rats were randomly divided into sham operation(SHAM)group,model(KOA)group,You Gui Wan low dose(KOA+YGWL)group,You Gui Wan medium dose(KOA+YGWM)group,You Gui Wan high dose(KOA+YGWH)group,positive control group of glucosamine sulfate(KOA+GS)group.Correspondence drug was intragastric administration in 6 weeks after modeling,samples were taken 8 weeks after intragastric administration,various techniques including Safranin O solid green staining,ELISA method,RT-PCR and Western blot were used to assess articular cartilage tissue morphology,changes of inflammatory cytokine levels in the serum,changes of HMGB1,RAGE,NF-κB gene and protein expression in the articular cartilage tissue.Results Our result suggest that the degree of joint cartilage injury,OARSI score,OARSI score,serum PGE2 levels,and expression of RAGE and NF-κB proteins in knee cartilage tissue were significantly lower in the KOA+YGWM group,KOA+YGWH group,KOA+GS group than that in the KOA group,the levels of IL-18,COX2 in the KOA+YGWL group,KOA+YGWM group,KOA+YGWH group,KOA+GS group were also significantly lower than that in the KOA group,as well as reduced gene expression of HMGB1,RAGE,and NF-κB in articular cartilage tissue,along with decreased HMGB1 protein expression(P<0.05 or P<0.01).The study result showed that the degree of joint cartilage injury,OARSI score,HMGB1 gene expression,and NF-κB and HMGB1 protein expression in articular cartilage tissue were significantly higher in the KOA+YGWL group than that in the KOA+GS group,the gene expressions of RAGE,NF-κB and the RAGE protein expression were also significantly higher in the KOA+YGWL group,KOA+YGWM group than that in the KOA+GS group,yet the gene expressions of RAGE,NF-κB were significantly lower in the KOA+YGWH group than that in the KOA+GS group(P<0.01).Conclusion You Gui Wan can alleviate joint cartilage tissue damage in KOA model,and its mechanism is closely related to inhibiting the secretion of downstream inflammatory factors of the HBGB1/RAGE/NF-κB signaling pathway,thereby suppressing the inflammatory response.
作者
颜春鲁
刘绪鹏
安方玉
肖小龙
张捷
师霞
隋创委
贾雪茹
彭霞
郁娟
YAN Chunlu;LIU Xupeng;AN Fangyu;XIAO Xiaolong;ZHANG Jie;SHI Xia;SUI Chuangwei;JIA Xueru;PENG Xia;YU Juan(Gansu University of Chinese Medicine,Lanzhou 730000,China;the Institute of Dunhuang Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Research Center of Traditional Chinese Medicine,Gansu Province,Lanzhou 730000,China)
出处
《中国骨质疏松杂志》
北大核心
2026年第1期33-39,共7页
Chinese Journal of Osteoporosis
基金
甘肃省自然科学基金项目(24JRRA1026)
甘肃省联合科研基金项目(24JRRA879)
甘肃省教育厅高校教师创新基金项目(2025B-125)
定西市科技计划项目(DX2024BY017)
甘肃省中医药研究中心开放课题(zyzx-2024-zx16)
甘肃中医药大学教学研究与改革项目(YBXM-202332)。
