豨桐丸对大鼠痛风性关节炎的影响及机制

Effect and Mechanism of Xitongwan on Gouty Arthritis Induced by Monosodium Urate in Rats

目的：观察豨桐丸对尿酸钠晶体诱导的大鼠痛风性关节炎的影响及其药理机制。方法：分别给予大鼠豨桐丸（200,400,800 mg·kg^-1）及秋水仙碱（4 mg·kg^-1）灌胃用药7 d。第5天大鼠踝关节腔注射尿酸钠晶体诱导痛风性关节炎模型。检测大鼠足肿胀和步态评分,苏木素-伊红（HE）染色法检测关节组织学评分,抗酒石酸酸性磷酸酶染色法检测破骨细胞形成,免疫组化法分析关节组织中肿瘤坏死因子（tumor necrosis factor,TNF）-α,白细胞介素（interleukin,IL）-1β和IL-6表达,蛋白免疫印迹法（Western blot）分析NLRP3炎性体表达。结果：注射尿酸钠晶体导致了大鼠明显的足肿胀,并使步态评分和组织学评分均明显增高,关节组织中的破骨细胞数量及TNF-α,IL-1β,IL-6和NLRP3炎性体表达也都明显增加（（P〈0.05,P〈0.01）。给予400,800 mg·kg^-1豨桐丸治疗后,大鼠足肿胀显著减轻,步态评分和组织学评分均显著减少,同时关节组织中的破骨细胞数量及TNF-α,IL-1β,IL-6和NLRP3炎性体表达也都显著降低（P〈0.05,P〈0.01）。结论：豨桐丸可抑制尿酸钠晶体诱导的大鼠痛风性关节炎的发展,其机制与抑制炎性介质的表达密切相关。

Objective： To observe the effect and pharmacological mechanism of Xitongwan on monosodium urate（ MSU）-induced gouty arthritis. Method： Rats were intragastrically treated with Xitongwan（ 200,400,800 mg·kg-1） for consecutively 7 days. MSU-induced gouty arthritis in rats was prepared through intra-articular injection with MSU crystals in the left ankle joint on the 5 thday. Paw volume was measured at 0,6,12,24,48 h,as well as gait score was calculated at 24 h after MSU induction. Histological score in ankle joint was calculated by hematoxylin and eosin staining. Osteoclast formation in ankle joint was detected by tartrateresistant acid phosphatase（ TRAP） staining. Expressions of tumor necrosis factor（ TNF）-α,interleukin（ IL）-1β,IL-6 and nucleotide-binding domain and leucine-rich repeat region containing family of receptor protein 3（ NLRP3） in articular tissues were analyzed by immunohistochemistry staining or Western blot assay. Result： Intraarticular injection with MSU crystals led to apparently elevated paw volume and gait score compared with control rats. Meanwhile,histological score,osteoclast formation and expressions of TNF-α,IL-（-1）β,IL-6 and NLRP3 of gouty arthritis rats were significantly increased compared with control rats. However,treatment with Xitongwan significantly alleviated paw volume and decreased gait score in gouty arthritis rats compared with control rats.Meanwhile,treatment with Xitongwan significantly reduced histological score,osteoclast formation and expressions of TNF-α,IL-（-1）β,IL-6 and NLRP3 in gouty arthritis rats compared with control rats. Conclusion： Xitongwan could attenuate the inflammatory development and structural damage by inhibiting the production of inflammatory mediators in gouty arthritis rats.