长期服用别嘌醇缓释胶囊对高尿酸血症大鼠肾脏的影响

目的考察长期服用别嘌醇缓释胶囊对高尿酸血症大鼠肾脏改变的影响和机制。方法 90只雄性Wistar大鼠随机分为正常对照组(10只),模型组(16只),别嘌醇缓释胶囊低、高(27、54 mg·kg~(-1)·d~(-1))剂量组(各16只),别嘌醇片低、高(32、64 mg·kg~(-1)·d~(-1))剂量组(各16只),采用腺嘌呤和乙胺丁醇连续灌胃3wk,3 wk后改为隔日1次,共12 wk造成大鼠高尿酸血症。在造模的同时,药物治疗组分别给予低、高剂量的别嘌醇缓释胶囊或别嘌醇片;在wk 12末,处死大鼠,取血和肾脏组织,检测血尿酸、肾脏功能及肾组织的TNF-α表达情况和观察肾脏形态、病理学变化。结果与正常对照组比较,模型组大鼠血尿酸、尿素氮含量和肾脏组织内TNF-α表达增加,肾脏含水量显著增加(P<0.05)。与模型组比较,别嘌醇缓释胶囊高剂量组显著降低大鼠血尿酸、血尿素氮含量和肾脏组织内TNF-α表达(P<0.05);低剂量组能显著降低肾组织含水量(P<0.05);肌酐含量和肾脏指数无明显差异(P>0.05)。与别嘌醇片高剂量组比较,别嘌醇缓释胶囊组降低肾脏指数和肾组织含水量有显著差异(P<0.05,P<0.01)。结论长期应用别嘌醇缓释胶囊治疗高尿酸血症能减缓肾脏的病理改变,其机制可能与其降低血尿酸水平的同时抑制TNF-α介导的炎症反应有关。

Effects of allopurinol sustained-release capsules on kidney in hyperuricacidemia rats by long term administration

AIM To investigate the protective effects of allopurinol sustained-release capsules(ASRC) on kidney in hyperuricacidemia rats by long term administration.METHODS Ninety Wistar rats were randomized into control group(n= 10),model group(n = 16),ASRC groups(27,54 mg·kg~(-1)·d~(-1),n = 16 each group),and allopurinol tablet groups(32,64 mg·kg~(-1)·d~(-1),n = 16 each group).Hyperuricemia model was induced by introgastric administration to rats with adenine and ethambutol for 12 weeks.Drug administration was started at the same time.Serum uric acid concentration was measured,the functional and pathological changes in kidney were observed,and the expression of TNF-αin kidney was evaluated.RESULTS Compared with control group,the concentration of serum uric acid(UA) and blood urea nitrogen(BUN),the expression of TNF-αin kidney,and the water content of renal tissue increased significantly in the model group(P<0.05). Compared with the model group,the concentration of serum UA and BUN,and the expression of TNF-αin kidney decreased significantly in high-dose ASRC group(P<0.05),the water content of renal tissue decreased significantly in low-dose ASRC group(P<0.05).There were no significant differences in serum creatinine levels and kidney index(P>0.05).Compared with high-dose allopurinol tablet group,the kidney index and water content of renal tissue decreased significantly in ASRC groups(P<0.05,P<0.01).CONCLUSION Long-term administration of ASRC has protective effects for kidney in hyperuricacidemia rats,which might be related to reducing serum uric acid levels and restraining the inflammatory response induced by TNF-α.