季德胜蛇药片治疗急性痛风性关节炎大鼠的机制研究  

Mechanism of Jidesheng snake tablets in the treatment of rats with acute gouty arthritis

作　　者：张楠[1] 张海骏 范艳艳 ZHANG Nan;ZHANG Haijun;FAN Yanyan(Emergency Department,Nantong Hospital of Traditional Chinese Medicine,Nantong,Jiangsu 226000,China;Laboratory Animal Center,Nantong University,Nantong,Jiangsu 226000,China)

机构地区：[1]南通市中医院急诊科,江苏南通226000 [2]南通大学实验动物中心,江苏南通226000

出　　处：《安徽医药》2025年第2期253-257,I0001,共6页Anhui Medical and Pharmaceutical Journal

基　　金：南通市市级科技计划指导性项目(JCZ20201)。

摘　　要：目的探究季德胜蛇药片治疗急性痛风性关节炎(AGA)大鼠的可能机制。方法2022年10月至2023年2月,选取60只雄性SD大鼠为研究对象,采用随机数字表法分为空白对照组、模型组、季德胜蛇药片组和依托考昔组,除空白对照组外其他大鼠均通过关节腔注射尿酸钠溶液构建AGA大鼠模型,造模成功后12 h,季德胜蛇药片组灌胃季德胜蛇药片2.4 g·kg^(−1)·d^(-1),依托考昔组灌胃依托考昔3.125 mg·kg^(−1)·d^(-1),均持续干预7 d,测量各组大鼠关节肿胀程度、步态行为学分级,并于末次干预12 h后腹主动脉取血采用酶联免疫吸附法测量血清白细胞介素-1β(IL-1β)、IL-6、IL-10及肿瘤坏死因子(TNF-α)水平;麻醉处死大鼠后分离踝关节滑膜组织固定后制成切片HE染色观察病理形态学特征,蛋白质印迹法检测滑膜组织中核转录因子-κB p65(NF-κB p65)、IL-1β、IL-6、IL-10、TNF-α蛋白表达水平。结果与空白对照组比较,模型组造模后1、2、3 d时关节肿胀度均升高,且步态行为学分级程度也升高(P<0.05),与模型组比较,季德胜蛇药片组与依托考昔组大鼠关节肿胀度均降低,步态行为学分级程度也有改善(P<0.05)。HE染色结果显示,模型组大鼠可见明显滑膜组织增生,充血水肿并伴有大量中性粒细胞及单核细胞等炎症细胞浸润,季德胜蛇药片干预后滑膜层细胞基本正常,轻微充血水肿,炎症细胞浸润程度降低,与依托考昔干预后情况基本一致。模型组大鼠血清IL-1β、IL-6、TNF-α水平[(45.15±8.76)ng/L、(54.26±8.29)ng/L、(229.54±31.18)ng/L]均高于空白对照组大鼠[(10.41±3.25)ng/L、(16.52±4.13)ng/L、(108.94±21.26)ng/L,P<0.05],滑膜组织中p-NF-κB p65/NF-κB p65、IL-1β、IL-6、TNF-α蛋白表达(1.98±0.32、1.34±0.12、1.20±0.18、1.30±0.11)均高于空白对照组大鼠(0.32±0.07、0.18±0.03、0.28±0.05、0.24±0.04,P<0.05),血清、滑膜组织IL-10水平和蛋白表达[(21.06±4.39)ng/L、0.72Objective To explore the possible mechanism of Jidesheng snake tablets in the treatment of rats with acute gouty arthritis(AGA).Methods A total of 60 male SD rats were enrolled as the research objects from October 2022 to February 2023,which were randomly assigned into blank control group,model group,Jidesheng snake tablets group and etoricoxib group.Except blank control group,rats were given intra-articular injection of sodium urate solution to construct models of rats with AGA in the other groups.At 12 h after successful modeling,Jidesheng snake tablets group was given intragastric administration of Jidesheng snake tablets(2.4 g·kg^(−1)·d^(-1)),while etoricoxib group was given intragastric administration of etoricoxib(3.125 mg·kg^(−1)·d^(-1)),and both for 7 d.The severity of joint swelling and behavioral grading of gait were measured.At 12 h after the last intervention,the blood of abdominal aorta was collected to detect levels of serum interleukin-1β(IL-1β),IL-6,IL-10 and tumor necrosis factorα(TNF-α)by enzyme-linked immunosorbent assay.After the rats were killed under anesthesia,synovial tissues of ankle joints were made into slices to observe pathomorphological charac⁃teristics by HE staining.The expression levels of nuclear transcription factorκB p65(NF-κB p65),IL-1β,IL-6,IL-10 and TNF-αpro⁃tein in synovial tissues were detected by Western blotting.Results Compared with blank control group,severity of joint swelling was increased in model group at 1 d,2 d and 3d after modeling,and behavioral grading of gait was also increased(P<0.05).Compared with model group,severity of joint swelling was decreased,and behavioral grading of gait was improved in Jidesheng snake tablets group and etoricoxib group(P<0.05).The results of HE staining showed that there was obvious synovial tissue hyperplasia,hyperemia and edema accompanied by inflammatory cells(neutrophils,monocytes)infiltration in model group.After intervention with Jidesheng snake tab⁃lets,synovial cells were basically normal.There was mi

关 键 词：急性痛风性关节炎 季德胜蛇药片 炎症因子 核转录因子-ΚB 大鼠 

分 类 号：R285.5[医药卫生—中药学]