目的 观察不同剂量的双醋瑞因对急性痛风性关节炎大鼠模型的防治作用并探讨其可能的机制.方法 选取Wista大鼠30只,随机数字表法分为正常对照组、阴性(0.9%氯化钠注射液)对照组、阳性(秋水仙碱)对照组、双醋瑞因低剂量组、中剂量组和高剂量组.除正常对照组外,分别给予0.9%氯化钠注射液、秋水仙碱(0.3 mg·kg-1·d-1)、双醋瑞因(10、50及100 mg· kg-1·d-1灌胃8d,并于第6天制备急性痛风性关节炎模型.分别于造模后2、6、8、24及48 h观察各组大鼠关节肿胀情况及步态.48 h后处死大鼠,留取血清及关节组织浸出液,检测IL-1β和TNF-α水平.采用单因素方差分析、两两比较采用LSD-t检验和Kruskal-Wallis秩和检验进行数据分析.结果 与正常对照组相比,阴性对照组大鼠造模后2h即出现明显关节肿胀,8h时达到高峰,之后逐渐下降,48 h后明显缓解.秋水仙碱组及双醋瑞因高剂量组关节肿胀情况[(0.106±0.081) cm和(0.112±0.030) cm]及踝关节炎症指数评分[(2.8±1.7)和(3.2±0.8)]在8h均较阴性对照组显著减轻[(0.208±0.078) cm,(4.7±1.6) cm;F=7.552,F=1.859,P均<0.05].此外,与阴性对照组比较,双醋瑞因高剂量组大鼠步态明显好转(P<0.05).秋水仙碱组和双醋瑞因高剂量组血清及关节浸出液中TNF-α及IL-1β水平均较照组明显降低.结论 双醋瑞因各剂量组对痛风性关节炎大鼠都有一定的防治作用,且以高剂量组疗效为佳,其抗炎机制可能是通过下调前炎症介质IL-1β和TNF-α的表达来发挥作用的.
Objective To observe the preventive effect of different doses of diacerein on acute gout model rats and to explore its possible mechanism.Methods A total of 30 Wistar rats and were randomly assigned to the normal control group, the negative control (normal saline control group, and positive (colchicine) control group, diacerein low dose group, medium iddle dose group and high dose group.Except the normal control group that were given normal saline, other groups received colchicine (0.3 mg·kg-1 ·d-1), diacerein (10 mg·kg-1·d-1, 50 mg·kg-1·d-1 and 100 mg·kg-1·d-1) for 8 days respectively, and prepared acute gouty arthritis model on the 6th day, then observed rats joint swelling and gait at 2 h, 6 h, 8 h, 24 h and 48 h after the acute gouty arthritis model were established.After 48 h, the rats were killed, the serum and joint leachate of the rats were collected to test interleukin (IL)-1β and tumor necrosis factor (TNF)-α.One-way analysis of variance (ANOVA), LSD t test and Kruskal-Wallis rank sum test were used for statistical analysis.Results Compared with the normal group, joint swelling of the rats in the negative control group became significantly swollen at 2 h after the model was established,at and it reached the peak at 8 h reached the peak, then decreased gradually and remitted obviously at 48 h obviously remission.Joint swelling of the ccolchicine group and diacerein high dose group joint swelling [(0.106±0.081) cm, (0.112±0.030) cm] and ankle joint inflammation index score [(2.8±1.7), (3.16±0.75)] were significantly decreased compared with the negative control group [(0.208±0.078) cm, (4.7±1.6);P〈0.05].In addition, compared with the negative control group, the gait of diacerein high dose group was significantly improved (F=7.552, F=1.859, P〈0.05), colchieine group and diacerein high dose group, the serum and joint leaching liquid TNF-α and IL-1 levels also decreased significantly (P〈0.05).Conclusion Diacerein in any In each d