槲皮素对痛风性关节炎大鼠的治疗作用及肾功能的影响

The therapeutic effect of quercetin on gouty arthritis and its influence in renal function in rats

目的探讨槲皮素对急性痛风性关节炎大鼠的治疗作用及其对肾功能的影响。方法 70只雄性SD大鼠随机均分为空白对照组,模型组,秋水仙碱组(0.5 mg/kg),别嘌醇组(20 mg/kg),槲皮素低、中、高剂量组(100、200、400 mg/kg)。连续灌胃给药7 d,第5天采用微晶尿酸钠和次黄嘌呤法制备大鼠急性痛风性关节炎模型。造模前和造模后2、6、12、24和48 h用缚线法测取右后肢小腿踝关节同一部位周径,计算肿胀率;采用比色法、酶联免疫吸附法等测定大鼠血清中尿酸(UA),β2-微球蛋白(β2-MG),胱素C(Cys-C),尿素(Urea),肌酐(Cr)含量。脱颈处死大鼠,取肾脏称质量,计算肾脏指数。结果槲皮素、秋水仙碱、别嘌醇能够显著抑制痛风性关节炎大鼠踝关节肿胀率;造模后8 h,秋水仙碱、槲皮素组血清UA水平均高于空白对照组和别嘌醇组,别嘌醇组低于空白对照组;48 h后,除别嘌醇组血清UA水平明显低于其余组外,其余组间差异均无统计学意义。各组比较,空白对照组β2-MG、Cys-C水平最低,别嘌醇组Urea、Cr水平及肾脏指数均最高(均P<0.05)。结论槲皮素对急性痛风性关节炎大鼠有显著的抗炎作用,但造模可能导致肾功能不同程度的损害。槲皮素对轻度肾损伤未见明显的保护作用,别嘌醇给药后加重肾功能损伤。

Objective To investigate the therapeutic effect of quercetin on acute gouty arthritis and its influence in re- nal function in rats. Methods Seventy male Sprague-Dawley rats were randomly divided into normal control group, model group, colchicine group （0.5 mg/kg）, allopurinol group （20 mg/kg）, quereetin 100, 200 and 400 mg/kg groups （n=10 for each group）. Rats were administered various drugs by oral gavage once a day for seven consecutive days throughout the experi- ment. On the fifth day, the animal model of acute arthritis was set up by giving monosodium urate crystal combined with hypoxanthine. The inflammatory reaction was detected by measuring the circumference of fight hind leg anklejoint with a tie line method at 0, 2, 6, 12, 24 and 48 h. The swelling ratio was calculated. The serum levels of uric acid （UA）, β2-microglohulin （β2-MG）, cystatin C （Cys-C）, urea nitrogen （Urea） and creatinine （Cr） were detected by colorimetry and enzyme-linked im- munosorbent assay.Rats were sacrificed at the end of experiment, and the kidney was weighed and the renal index was calculated. Results Treatment with quercetin, colchicine or a11opurinol can significantly attenuate swelling rate in rats of acute gouty arthritis. The serum levels of UA were significantly higher in eolchieine group and quercetin group than those of nor- mal control group and allopurinol group. The serum levels of UA was significantly lower in allopurinol group than that of nor- mal control group. After 48-h modeling, there was no significant difference in serum UA level between seven groups except allopurinol group. The levels of β2-MG and Cys-C were the lowest in normal control group than those of other groups. The se- rum levels of Urea and Cr and renal index were the highest in allopurinol group compared with those of other groups （P 〈 0.05）. Conclusion Quercetin shows a significant effect of anti-inflammatory on acute gouty arthritis in rats. The model es- tablishment may lead to different degrees of renal damage. Quercetin has no protective effect against renal injury, and allopu- rinol aggravates kidney injury.