羌活醇对类风湿性关节炎大鼠OPG/RANKL/RANK通路及骨稳态的影响OA
Effect of Notopterol on the OPG/RANKL/RANK Pathway and Bone Homeostasis in Rats with Rheumatoid Arthritis
目的:探讨羌活醇对类风湿性关节炎(RA)大鼠骨保护素(OPG)/核因子 κB 受体活化因子配体(RANKL)/核因子 κB 受体活化因子(RANK)通路及骨稳态的影响.方法:大鼠随机分为对照组、RA 组、羌活醇低剂量组、羌活醇中剂量组、羌活醇高剂量组、雷公藤多苷组,每组 12 只.除对照组外,其他组大鼠均需构建 RA 模型.建模成功后给药,羌活醇低、中、高剂量组大鼠分别腹腔注射 3.33、6.66、13.32mg/kg 羌活醇;雷公藤多苷组大鼠灌胃 9mg/kg 雷公藤多苷;对照组和 RA 组大鼠同方式给予等量的生理盐水,处理1 次/d,持续4 周.检测足趾肿胀度、关节炎指数、机械性痛阈值、热缩足反射潜伏期变化;ELISA 检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-17、抗酒石酸酸性磷酸酶5b(TRAP-5b)、I 型胶原 C 端交联肽(CTX-Ⅰ)、骨特异性碱性磷酸酶(BALP)、I 型前胶原 N 端前肽(PINP)水平;HE 染色检测踝关节组织病理;抗酒石酸酸性磷酸酶 5b(TRAP-5b)染色检测踝关节组织中破骨细胞数;qRT-PCR、Western blot 分别检测踝关节组织中 OPG、RANKL、RANK、核因子 κB p65亚基(NF-κB p65)mRNA 及蛋白表达.结果:与对照组比较,RA 组大鼠关节炎性病变严重,足趾肿胀度、关节炎指 数、血清 TNF-α、IL-1β、IL-17、TRAP-5b、CTX-Ⅰ水平、踝关节组织中破骨细胞数、RANKL 和 RANK 的 mRNA 及蛋白表达、NF-κB p65 mRNA、p-NF-κB p65/NF-κB p65 蛋白表达升高,机械性痛阈值、热缩足反射潜伏期、血清 BALP、PINP 水平、踝关节组织中 OPG mRNA 表达及蛋白表达降低(P<0.05);与 RA 组比较,羌活醇低、中、高剂量组、雷公藤多苷组对应指标变化趋势与上述相反(P<0.05).结论:羌活醇可能通过调控 OPG/RANKL/RANK 通路恢复 RA 大鼠的骨稳态.
Objective:To investigate the effect of notopterol on the osteoprotegerin(OPG)/receptor ac-tivator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)pathway and bone homeostasis in rats with rheumatoid arthritis(RA).Methods:Rats were randomly divided into 6 groups(12 rats per group):control group,RA group,low-dose notopterol group,medium-dose notopterol group,high-dose notopterol group,and tripterygium glycosides group.RA model was constructed in all groups but the control group.After successful modeling and administration,rats in the low,medium,and high-dose no-topterol groups received intraperitoneal injections of 3.33,6.66,and 13.32mg/kg of notopterol,respective-ly;rats in the Tripterygium glycosides group received 9mg/kg of Tripterygium glycosides by gavage;and rats in the control group and RA group received an equal volume of normal saline via the same routes.All treat-ments were administered once daily for 4 consecutive weeks.The following indicators were detected:Changes in toe swelling,arthritis index,mechanical pain threshold,and thermal withdrawal latency;serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-17(IL-17),tartrate-resistant acid phosphatase 5b(TRAP-5b),C-terminal telopeptide of type I collagen(CTX-I),bone-specific alka-line phosphatase(BALP),and N-terminal propeptide of type I procollagen(PINP)by ELISA;pathological changes of ankle joint tissue by HE staining;number of osteoclasts in ankle joint tissue by tartrate-resistant acid phosphatase 5b(TRAP-5b)staining;mRNA and protein expressions of OPG,RANKL,RANK,and nuclear factor-κB p65 subunit(NF-κB p65)in ankle joint tissue by qRT-PCR and Western blot,respec-tively.Results:Compared with the control group,the RA group showed severe inflammatory lesions of arthri-tis,with significant increases in toe swelling,arthritis index,serum levels of TNF-α,IL-1β,IL-17,TRAP-5b,and CTX-I,number of osteoclasts in ankle joint tissue,mRNA and protein expressions of RANKL and RANK,mRNA expression of NF-κB p65,and the protein ratio of phosphorylated NF-κB p65(p-NF-κB p65)to total NF-κB p65(P<0.05).In contrast,the mechanical pain threshold,thermal withdrawal laten-cy,serum levels of BALP and PINP,and mRNA and protein expressions of OPG in ankle joint tissue were significantly decreased in the RA group(P<0.05).Compared with the RA group,the low-dose,medium-dose,and high-dose notopterol groups,as well as the tripterygium glycosides group,had the opposite trends in the above indicators(P<0.05).Conclusions:Notopterol may restore bone homeostasis in RA rats by reg-ulating the OPG/RANKL/RANK pathway.
李青松;宋丽园;谢大伟
北京中医药大学东方医院秦皇岛医院/秦皇岛市中医医院,河北 秦皇岛 066000北京中医药大学东方医院秦皇岛医院/秦皇岛市中医医院,河北 秦皇岛 066000北京中医药大学东方医院秦皇岛医院/秦皇岛市中医医院,河北 秦皇岛 066000
类风湿性关节炎羌活醇骨稳态炎症骨吸收骨生成
Rheumatoid arthritisNotopterolBone homeostasisInflammationBone resorp-tionBone formation
《河北医学》 2026 (7)
1077-1083,7
河北省医学科学研究课题计划资助(20261658)
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