甘草附子汤对风寒湿痹型痛风性关节炎小鼠的治疗作用及机制  

Therapeutic Effect and Mechanism of Licorice Aconite Decoction on Gouty Arthritis in Mice with Wind-cold-damp Obstruction

作　　者：刘小瑜 安丽萍[1] 王曼力[1] 王宝辉 王海珊 闫宇宁 林逢源 管芸卉 LIU Xiaoyu;AN Liping;WANG Manli;WANG Baohui;WANG Haishan;YAN Yuning;LIN Fengyuan;GUAN Yunhui(Pharmacy College of Beihua University,Jilin 132013,China)

机构地区：[1]北华大学药学院,吉林吉林132013

出　　处：《北华大学学报（自然科学版）》2024年第5期609-614,共6页Journal of Beihua University（Natural Science）

基　　金：吉林省科技攻关计划项目(2023C029-1)。

摘　　要：目的探讨甘草附子汤(Licorice aconite decoction,LA)对风寒湿痹型痛风性关节炎小鼠的治疗作用及机制。方法将40只ICR小鼠随机分为空白组(CON)、模型组(MOD)、非布司他组(Febuxostat,FBX,8 mg/(kg·d))和甘草附子汤组(LA,6.4 g/(kg·d))。同时建立风寒湿痹型痛风性关节炎小鼠模型,持续2周。观察小鼠关节肿胀情况;检测小鼠血清尿酸(uric acid,UA)、丙二醛(malondialdehyde,MDA)、过氧化氢酶(catalase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)水平;检测肝脏中黄嘌呤氧化酶(Xanthine oxidase,XOD)水平;采用ELISA试剂盒检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)水平;HE染色观察小鼠踝关节组织病理学情况;蛋白免疫印迹法(Western blot)检测小鼠踝关节组织中核因子κB(nuclear factor kappa-B,NF-κB)、蛋白激酶B(threonine protein kinase,AKT)、TNF-α、IL-1β蛋白表达水平。结果FBX组、LA组小鼠关节肿胀度均有不同程度的显著降低(P<0.05)。与MOD组比较,FBX组和LA组血清UA浓度、MDA、XOD、TNF-α、IL-1β水平降低(P<0.05),CAT、SOD水平显著升高(P<0.05)。HE染色结果显示,与CON组比较,MOD组小鼠关节炎性细胞浸润明显;与MOD组比较,FBX组和LA组炎性细胞浸润减轻,细胞形态相对光滑完整。Western blot结果显示,与MOD组比较,FBX组和LA组关节组织中NF-κB、AKT、TNF-α、IL-1β蛋白表达水平显著降低(P<0.05)。结论甘草附子汤对风寒湿痹型痛风性关节炎小鼠具有保护作用,其机制可能是通过改善模型小鼠体内氧化应激状态,抑制NF-κB/AKT信号通路激活,下调下游炎症因子TNF-α、IL-1β表达,达到减轻小鼠关节炎症的效果。Objective To investigate the effect of Licorice aconite decoction(LA)on gouty arthritis in mice with wind-cold-damp obstruction.Method Forty ICR mice were randomly divided into normal group(CON),model group(MOD),Febuxostat group(FBX,8 mg/(kg·d)),Licorice aconite decoction group(LA,6.4 g/(kg·d)).At the same time,gouty arthritis in mice model with wind-cold-damp obstruction was established,lasted two weeks.To observe the joint swelling in mice;The serum levels of uric acid(UA),malondialdehyde(MDA),catalase(CAT)and superoxide dismutase(SOD)were detected;Xanthine oxidase(XOD)level in liver was detected;By ELISA kit to detect serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)level.HE staining was used to observe the histopathological changes of ankle joints.Western blot was used to detect the expression of nuclear factor kappa-B(NF-κB),threonine protein kinase B(AKT),TNF-αand IL-1βprotein expression levels in the ankle joint of mice.Results The swelling degree of mice in the FBX group and the LA group was significantly reduced in different degrees(P<0.05).Compared with MOD group,the serum UA concentration,MDA,XOD,TNF-αand IL-1βlevels in the FBX and LA groups were significantly decreased(P<0.05),and the CAT and SOD levels were significantly increased(P<0.05).HE staining showed that compared with CON group,the infiltration of inflammatory cells in the joints of MOD group was more obvious.Compared with the MOD group,the inflammatory cell infiltration was reduced in FBX group and LA group,and the cell morphology was relatively smooth and complete.Western blot results showed that compared with MOD group,the protein expression levels of NF-κB,AKT,TNF-αand IL-1βin joint tissues were significantly decreased in FBX group and LA group(P<0.05).Conclusion Licorice aconite decoction has protective effect on gouty arthritis mice with wind-cold-damp obstruction.The mechanism may improve the oxidative stress state in the model mice,inhibit the activation of NF-κB/AKT signaling pathway,and down-regulate the expr

关 键 词：甘草附子汤 风寒湿痹型痛风性关节炎 氧化应激 炎症因子 

分 类 号：R22[医药卫生—中医基础理论] R285.5[医药卫生—中医学] R684R96