【摘要】 目的观察芍甘附子汤对胶原诱导性关节炎（CIA）大鼠的干预作用并探讨其作用机制。方法 Wistar大鼠随机选取12只为正常组,其余大鼠制备CIA大鼠模型。于首次免疫后第14日,依据分层分配原则将造模成功的大鼠分为模型组,芍甘附子汤低（1.05 g·kg-¹）、中（2.1 g·kg-¹）、高（4.2 g·kg-¹）剂量组,雷公藤多苷片组（9 mg·kg-¹）,每组15只。于首次免疫后第15日各组按相应剂量进行药物干预,正常组及模型组灌胃同等量生理盐水,连续4周。分别于首次免疫后第14、21、28、35、42日进行关节炎指数（AI）评分。于末次给药24 h后麻醉大鼠,收集血清,并取踝关节,采用HE染色和Micro-CT扫描观察其病理及影像学改变。检测血清PGE₂、TNF-α、IL-1β、IL-6、NO含量,免疫组织化学法检测踝关节组织PPAR-γ、NF-κB p65、p-NF-κB p65、COX-2、iNOS蛋白表达。结果同正常组相比,模型组大鼠足跖出现明显肿胀,血清PGE₂、TNF-α、IL-1β、IL-6、NO水平升高（P<0.01）,踝关节滑膜增生,炎细胞浸润,骨质破坏,踝关节NF-κB p65、p-NF-κB p65、COX-2、iNOS蛋白表达上调,PPAR-γ蛋白表达显著降低。同模型组相比,芍甘附子汤可不同程度降低AI,降低血清PGE₂、NO、TNF-α、IL-1β、IL-6水平,改善踝关节病理损害,降低病理评分,下调踝关节NF-κB p65、p-NF-κB p65、COX-2、iNOS蛋白表达,上调PPAR-γ蛋白表达。结论芍甘附子汤对CIA大鼠关节肿胀及病理损害具有改善作用,作用机制可能与其调节PPAR-γ/NF-κB信号通路有关。更多还原

【Abstract】 Objective To determine the intervention effect of Shaogan Fuzi decoction on rats with collagen-induced arthritis （CIA） and explore its mechanism.Methods Twelve SPF Wistar rats were randomly selected as the normal group,and the rest were turned into bovine type Ⅱ collagen induced arthritis rat models.According to the principle of stratified allocation,the CIA rats were divided into a model groups,Shaogan Fuzi decoction low-dose group （1.05 g·kg-¹）,medium-dose group （2.1 g·kg-¹）,high-dose group （4.2 g·kg-¹）,and a tripterygium glycoside tablet group （9 mg·kg-¹）,with 15 rats in each group.On the 15th day after primary immunization,each group was given drug intervention.The normal group and the model group were given the same dose of normal saline for 4 consecutive weeks.The arthritis index （AI） score was collected on day 14,21,28,35,and 42.The rats were anesthetized 24 hours after the last administration.The serum was collected,and the ankle joint was taken.HE stained and Micro-CT scan were used to observe the pathological and imaging changes.Content of PGE₂,TNF-α,IL-1β,IL-6,and NO in the serum was determined.PPAR-γ,NF-κB p65,p-NF-κB p65,COX-2,iNOS protein expression in ankle joint tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group had obvious feet swelling,and levels of PGE₂,TNF-α,IL-1β,IL-6,and NO in the serum were increased （P<0.01）.The ankle synovial hyperplasia,inflammation cell infiltration,bone destruction,and up-regulation of ankle joint NF-κB p65,p-NF-κB p65,COX-2,and iNOS protein expression were observed,but PPAR-γ protein expression was significantly reduced.Compared with the model group,Shaogan Fuzi decoction reduced the AI score,the serum levels of PGE₂,NO,TNF-α,IL-1β,and IL-6,improved the pathological damage of the ankle joint,decreased the pathological score,and down-regulated protein expression of the ankle joint NF-κB p65,p-NF-κB p65,COX-2,and iNOS,but up-regulated the expression of PPAR-γ protein.Conclusion Shaogan Fuzi decoction can improve the AI and pathological damage in CIA rats,whose mechanism of action may be related to the regulation of PPAR-γ/NF-κB signaling pathway.更多还原