目的 研究活血止痛胶囊对骨关节炎（osteoarthritis，OA）大鼠的药效作用。方法 采用改良Hulth法诱导大鼠OA模型，造模后大鼠随机分为模型组、盘龙七片（283 mg/kg）组、塞来昔布（18 mg/kg）组和活血止痛胶囊低、中、高剂量（135、270、540 mg/kg）组，每组10只，另取10只正常大鼠作为对照组。给予药物干预30 d后，从疼痛阈值、步态行为、骨微结构、膝关节病理、氧化应激水平、炎症因子水平以及相关功能蛋白的表达评价活血止痛胶囊对OA大鼠的药效作用。结果 与模型组比较，活血止痛胶囊组大鼠机械性反射阈值显著升高（P＜0.001），足印长度、足趾宽度和足印面积显著减少（P＜0.05、0.01、0.001），膝关节骨小梁数量、骨体积分数、各向异性程度和骨密度显著升高（P＜0.01、0.001），骨小梁分离度和结构模型指数明显降低（P＜0.05、0.01），血清和关节软骨组织中乳酸脱氢酶（lactate dehydrogenase，LDH）活性及丙二醛（malondialdehyde，MDA）水平显著降低（P＜0.05、0.01、0.001），还原性谷胱甘肽（glutathione，GSH）水平及超氧化物歧化酶（superoxide dismutase，SOD）活性显著升高（P＜0.05、0.01、0.001），大鼠血清和关节腔灌洗液中白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、前列腺素E₂（prostaglandin E₂，PGE₂）、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）水平显著降低（P＜0.05、0.01、0.001），软骨组织中II型胶原蛋白（Collagen Ⅱ）和基质金属蛋白酶抑制剂-1（tissue inhibitor of metalloprotease-1，TIMP-1）蛋白表达水平显著升高（P＜0.001），基质金属蛋白酶13（matrix metalloproteinases 13，MMP13）和聚蛋白多糖酶5（a disintegrin and metalloproteinase with thrombospondin motifs 5，ADAMTS5）蛋白表达水平显著降低（P＜0.001），大鼠软骨损伤和退变、滑膜炎症反应得到不同程度的改善。结论 活血止痛胶囊能够通过改善OA大鼠疼痛阈值、步态行为、关节骨微结构改变、软骨损伤、抗氧化因子、抗炎因子及功能蛋白的表达，从而发挥治疗OA的作用。

Objective To study the therapeutic efficacy of Huoxue Zhitong Capsule (活血止痛胶囊, HXZT) on osteoarthritis (OA) rats. Methods The model of rats with OA was induced by improved Hulth method. After modeling, the rats were randomly divided into model group, Panlongqi Tablet (PL, 283 mg/kg) group, celecoxib (CEL, 18 mg/kg) group, HXZT low-, medium- and high-dose (135, 270, 540 mg/kg) groups, with 10 rats in each group, and 10 normal rats were selected as the control group. After 30 d of drug intervention, the pharmacodynamic effect of HXZT on OA rats was evaluated from the pain threshold, gait behavior, bone microstructure, knee joint pathology, oxidative stress level, inflammatory factor level and expressions of related functional proteins. Results Compared with model group, the mechanical reflex threshold of rats in HXZT group was significantly increased (P < 0.001), the length of footprints, the width of toes and the area of footprints were significantly decreased (P < 0.05, 0.01, 0.001), the number of trabecular bones, bone volume fraction, anisotropy and bone mineral density of knee joints were significantly increased (P < 0.01, 0.001), and the trabecular separation and structural model index were significantly decreased (P < 0.05, 0.01). The activity of lactate dehydrogenase (LDH) and the level of malondialdehyde (MDA) in serum and articular cartilage tissues were significantly decreased (P < 0.05, 0.01, 0.001), and the level of glutathione (GSH) and the activity of superoxide dismutase (SOD) were significantly increased (P < 0.05, 0.01, 0.001). The levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E₂ (PGE₂) and inducible nitric oxide synthase (iNOS) in serum and joint lavage fluid of rats were significantly decreased (P < 0.05, 0.01, 0.001). The protein expression levels of collagen II and tissue inhibitor of metal protease-1 (TIMP-1) in cartilage tissue were significantly increased (P < 0.001), while matrix metalloproteinases 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were significantly reduced (P < 0.001). Cartilage injury and degeneration and synovial inflammation were improved to varying degrees in rats. Conclusion HXZT can play a role in the treatment of OA by improving pain threshold, gait behavior, alterations in joint bone microstructure, cartilage damage, antioxidant factors, anti-inflammatory factors and expressions of functional proteins in OA rats.

R285.5