白虎加桂枝汤对急性痛风性关节炎大鼠TLRs和NALP3信号通路的影响

Effects of Baihu Plus Guizhi Decoction(白虎加桂枝汤)on TLRs and NALP3 Signaling Pathways in Rats with Acute Gouty Arthritis

目的分析白虎加桂枝汤对急性痛风性关节炎(acute gouty arthritis,AGA)大鼠TLRs和NALP3信号通路的影响。方法于SD大鼠右侧踝关节处注入200μL尿酸钠溶液以构建AGA模型,本研究中最终成功构建40只AGA大鼠模型。将造模成功的大鼠随机分为模型组、低剂量组(0.265 g/100 g)、中剂量组(0.53 g/100 g)、高剂量组(1.06 g/100 g),每组各10只,并纳入10只健康SD大鼠为对照组,低剂量组、中剂量组、高剂量组大鼠分别灌胃不同剂量的白虎加桂枝汤,模型组和对照组灌胃等体积生理盐水,各组均连续灌胃7 d,并标准饲养。比较各组大鼠不同时刻踝关节周长、尿酸、血肌酐、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平、步态评分和滑膜组织中NALP3、TLRs相关蛋白及其mRNA表达水平。结果灌胃1、3、7 d时对照组大鼠的踝关节周长、尿酸、血肌酐、IL-1β、TNF-α水平、步态评分最低,且呈现剂量反应(P<0.05)。灌胃1、3、7 d时对照组大鼠滑膜组织中NALP3、TLR3、TLR7蛋白表达及其mRNA表达最低,且呈现剂量反应(P<0.05)。结论白虎加桂枝汤能够改善AGA大鼠的炎症反应,改善肾功能,减轻踝关节组织病理损伤,其机制可能与抑制TLRs和NALP3信号通路相关。

Objective To investigate the effects of Baihu Plus Guizhi Decoction(白虎加桂枝汤)on Toll-like receptors(TLRs)and NALP3 signaling pathway in rats with acute gouty arthritis(AGA).Methods The AGA model was constructed by injecting 200μL sodium urate solution at the right ankle joint of SD rats.In this study,40 AGA rat models were successfully constructed.The rats were randomly divided into model group,low dose group(0.265 g/100 g),medium dose group(0.53 g/100 g)and high dose group(1.06 g/100 g),with 10 rats in each group,and 10 healthy SD rats were included as the control group.The rats in low-dose group,medium-dose group and high-dose group were given different doses of Baihu Plus Guizhi Decoction by intragastric administration,while the rats in the model group and the control group were given the equal volume of normal saline by intragastric administration.The rats in each group were given intragastric administration for 7 days,and were fed with standard feeding.The ankle circumference,uric acid,serum levels of creatinine,interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),gait score,and the expression levels of NALP3 and TLRs related proteins and mRNA in synovial tissue were compared among the groups at different times.Results The ankle circumference,uric acid,serum levels of creatinine,IL-1βand TNF-αand gait score were the lowest in the control group at day 1,3 and 7,and showed dose response(P<0.05).The protein and mRNA expressions of NALP3,TLR3 and TLR7 in synovial tissues of the rats in the control group were the lowest on day 1,3 and 7 by gavage,and showed dose response(P<0.05).Conclusion Baihu Plus Guizhi Decoction can improve the inflammatory response,renal function and pathological injury of ankle joint in AGA rats,and its mechanism may be related to the inhibition of TLRs and NALP3 signaling pathway.