Objective: A modified method was used to establish acute gouty arthritis (AGA) rat model. The major symptoms, including ankle joint inflammation and pain of AGA rats as well as the analgesic effect of indomethacin were evaluated. Methods: Twenty-four male SD rats were randomly divided into Vehicle group and MSU group (n = 12) in Experiment #1. Rats of MSU group were injected with 1.25 mg/50 μl monosodium urate in the rear side of left ankle in 30-40°angle, following the interior side of Achilles tendon. Rats of Vehicle group were injected with the same volume of phosphate buffered saline. The ankle swelling of these two groups was measured before model establishment and 2, 4, 8, 24 and 48 h thereafter. Animal behavioral assay was further used to evaluate the nocifensive behavior, which included ongoing pain score, mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL).Twelve male SD rats were randomly divided into MSU group and Vehicle group in Experiment #2 .The pathological changes of ankle synovial tissue were evaluated at 24 h after model establishment. Eighteen male SD rats were randomly divided into MSU group, Vehicle group and Treatment group (n = 6) in Experiment #3. After the successful establishment of the model, the therapeutic effect of indomethacin on PWT was further evaluated 4, 8, 24 h thereafter.Results: 2 h after the model establishment, the MSU group showed obvious ankle joint swelling compared with Vehicle group in Experiment #1. The swelling lasted up to 48 h. The MSU group showed obvious ongoing pain behavior and the PWT began to decline significantly 2 h after model establishment (P < 0.05). PWL also exhibited significant decline (P < 0.05), 4 h after the model establishment. These pain-related behaviors remained until 24 h after the model establishment (P < 0.01). MSU group showed extensive inflammatory cell infiltration in Experiment #2. Furthermore, indomethacin significantly alleviated the mechanical hyperalgesia of the MSU rats (P < 0.05) in Experiment #3. Conclusions: The modified model of AGA is simple and shows good reproducibility. It induces obvious ankle swelling and pain-related behavior in tested rats, which are the major clinical manifestations of AGA. Therefore, our results suggest that this modified method can be used to establish animal models of AGA and can be further used for screening of potential analgesic drugs.%目的:采用一种改良方法制备急性痛风性关节炎大鼠模型,并对造模后大鼠出现的急性痛风性关节炎的主要症状,即关节局部炎症和疼痛进行分析和评价.最后验证吲哚美辛是否能够对该模型大鼠发挥有效镇痛作用.方法:实验一:把24只雄性SD大鼠采用随机数字表法分为模型组和对照组(n=6).模型组大鼠左踝后侧沿跟腱内侧以30~40°方向穿刺关节腔,注射1.25 mg/50μl尿酸钠,制备大鼠急性痛风性关节炎模型.对照组则以同样方式注射等量磷酸盐缓冲液.对两组大鼠造模前及造模后的2 h,4 h,8 h,24 h和48 h踝关节肿胀程度测量,进一步利用动物行为学方法对大鼠疼痛行为学指标进行检测,包括自发性疼痛行为评分、机械缩爪阈值和热痛敏潜伏期.实验二:将12只雄性SD大鼠随机分为模型组和对照组(n=6),造模后24 h对其踝关节滑膜组织进行病理学分析.实验三:把18只雄性SD大鼠随机分为模型组、对照组和治疗组(n=6).模型成功建立后,进一步利用行为学方法观察腹腔注射吲哚美辛后对模型大鼠4 h,8 h,24 h机械缩爪阈值的影响.结果:实验一:利用改良法造模2 h后,与对照组相比,模型组大鼠踝关节开始出现明显肿胀,模型组踝关节肿胀情况可持续48 h以上.造模2 h后,模型组大鼠开始出现自发性疼痛行为,并且机械缩爪阈值开始出现显著降低(P<0.05).造模4 h后,热痛敏潜伏期也开始出现显著下降(P<0.05).模型组大鼠上述各项疼痛指标一直持续到模型建立后的第24 h(P<0.01).实验二:模型组大鼠踝关节滑膜组织相比对照组出现广泛炎性细胞浸润.实验三:吲哚美辛可以有效缓解该模型大鼠机械痛过敏情况(P<0.05).结论:采用该改良方法制备急性痛风性关节炎大鼠模型方法简单,重现性好,可引发大鼠出现明显关节炎症及疼痛等急性痛风性关节炎表现的主要临床症状.并且非甾体抗炎药对该模型可发挥显著镇痛作用.因此提示这一方法可用于急性痛风性关节炎动物模型制备,并用于镇痛药物的筛选,值得进一步推广.
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