目的 基于Toll样受体4（Toll-like receptor 4，TLR4）/核因子-κB（nuclear factor-κB，NF-κB）信号通路探讨淫羊藿苷改善肾虚血瘀型膝骨关节炎（knee osteoarthritis，KOA）大鼠关节炎症的作用及机制。方法 将60只雌性SD大鼠随机分为对照组、模型组、阳性对照（仙灵骨葆胶囊270 mg/kg）组和淫羊藿苷低、中、高剂量（40、100、200 mg/kg）组，每组10只。除对照组外，其余各组采用“去卵巢法＋氢化可的松联合肾上腺素法＋改良Hulth法”复合制备肾虚血瘀型KOA大鼠模型。造模成功后，各组连续ig给药4周。分别于给药0、1、2、3、4周检测大鼠关节炎症评分及关节肿胀度；给药结束后，ELISA法检测血清中白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和IL-10水平，苏木素-伊红（hematoxylin-eosin，HE）染色观察膝关节软骨病理变化，Western blotting检测软骨组织TLR4、髓样分化因子88（myeloid differentiation factor 88，MyD88）、NF-κB抑制蛋白（inhibitor of NF-κB，IκB）、p-IκB、NF-κB p65、p-NF-κB p65蛋白表达。结果 与对照组比较，模型组大鼠关节炎症评分和关节肿胀度显著升高（P＜0.001），血清中IL-1β、IL-6、TNF-α水平显著升高（P＜0.001），IL-10水平显著降低（P＜0.001），软骨组织病理损伤明显，软骨组织TLR4、MyD88、p-IκB、p-NF-κB p65蛋白表达水平显著升高（P＜0.05、0.01、0.001）。与模型组比较，阳性对照组及淫羊藿苷中、高剂量组上述指标均有不同程度的改善，淫羊藿苷低剂量组部分指标呈改善趋势。结论 淫羊藿苷可改善肾虚血瘀型KOA大鼠关节炎症及软骨损伤，其机制可能与抑制TLR4/NF-κB信号通路活化、调控炎症因子网络平衡有关。

Objective To explore the effect and mechanism of icariin in improving knee osteoarthritis (KOA) in rats with kidney deficiency and blood stasis based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods A total of 60 female SD rats were randomly divided into control group, model group, positive control [Xianling Gubao Capsules (仙灵骨葆胶囊, 270 mg/kg)] group and icariin low-, medium-, high-dose (40, 100, 200 mg/kg) groups, with 10 rats in each group. Except for the control group, the other groups were prepared with a combination of “ovariectomy method + hydrocortisone combined with adrenaline method + modified Hulth method” to establish a kidney deficiency and blood stasis KOA rat model. After successful modeling, each group was administered ig continuously for four weeks. The joint inflammation score and joint swelling degree of rats were measured at 0, 1, 2, 3, and 4 weeks after administration. After administration, the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and IL-10 in serum were detected by ELISA. Hematoxylin-eosin (HE) staining was used to observe pathological changes in knee cartilage. Western blotting was used to detect the expressions of TLR4, myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB (IκB), p-IκB, NF-κB p65 and p-NF-κB p65 proteins in cartilage tissue. Results Compared with control group, the joint inflammation score and joint swelling degree of rats in model group were significantly increased (P < 0.001), the levels of IL-1β, IL-6, TNF-α in serum were significantly increased (P < 0.001), and the level of IL-10 was significantly decreased (P < 0.001). The pathological damage of cartilage tissue was obvious, and the protein expression levels of TLR4, MyD88, p-IκB, p-NF-κB p65 in cartilage tissue were significantly increased (P < 0.05, 0.01, 0.001). Compared with model group, the positive control group and icariin medium-, high-dose groups showed varying degrees of improvement in the above indicators, while some indicators in icariin low-dose group showed an improvement trend. Conclusion Icariin could improve joint inflammation and cartilage damage in KOA rats with kidney deficiency and blood stasis, and its mechanism may be related to inhibiting the activation of TLR4/NF-κB signaling pathway and regulating the balance of inflammatory cytokine network.

R285.5

国家自然科学基金资助项目（82575103）；国家自然科学基金资助项目（82474538）；国家自然科学基金资助项目（82074470）；天津市卫生健康委员会天津市中医药重点领域科研项目（2026005）；河北省中医药管理局科研计划项目（T2025087）；天津中医药大学教师队伍建设研究项目（Y-202608）；天津中医药大学教师教学发展研究项目（A26JF12）；天津市高等学校研究生教育改革研究计划项目（TJYG25101）