Objective To study the influences of long term administration of allopurinol sustained-release capsules (ASRC) on blood system in rats with hyperuricacidemia. Methods 90 Wistar rats were randomly divided into 6 groups; the normal control, hyperuricacidemia model control, ASRC treatment groups (27, 54 mgokg-1 o d-1 ) , allopurinol tablet treatment groups (32, 64 mg o kg-1 o d-1 ). There were 10 rats in the normal control group and 16 rats in each of the other groups. The hyperuricemia rats model was created by continually intragastric (i. g) treatment with adenine and ethambutol hydrochloride for 3 weeks, and then changing administration to every other day till 12 weeks. The body weight of rats were monitored periodically. By the end of 12 weeks, the serum level of uric acid (UA) and peripheral hemogram were assayed, the bone marrow smear was examed, IL-lp secretion was checked and renal tissue sections were checked under a light microscope by PAS staining. Results Compared with the normal control, the serum level of UA, the count of WBC and PLT were remarkably increased, while the weigth of rats and the count of RBC were sharply reduced. The serum level of IL-lp was obviously increased too, and the inflammatory cells infiltration was found in renal tissues of the model rats. Compared with the model control, the ASRC at low-dose increased the count of RBC, decreased WBC and PLT (P<0. 05 ) , and effectively suppressed 1L-1 β secretion. The ASRC at high-dose inhibited the weight loss of hyperuricemia rat, decreased the content of serum UA and IL-lβ. Only a few inflammatory cell infiltration was found in renal interstitial. Conclusion Long-term administration of ASRC at low-dose can reverse abnormal changes of peripheral hemogram in hyperuricacidemia rats, which is related to its effectively restraining the inflammatory response induced by IL-lβ and slight changes of renal structure. The ASRC at high-dose could more effectively lower serum level of UA, which suggests that attentions should be paid to the dose in clinic uses.%目的 研究长期(3个月)灌服用别嘌醇缓释微丸胶囊(ASRC)治疗大鼠高尿酸血症时对血液系统的影响.方法 雄性Wistar大鼠90只,随机分为正常对照组,模型组,别嘌醇缓释微丸胶囊低、高剂量组(给予别嘌醇缓释微丸胶囊27,54 mg·kg-1·d-1),别嘌醇低、高剂量组(给予别嘌醇32,64 mg·kg-1·d-1).除正常对照组10只,其余各组增加6只,采用腺嘌呤和乙胺丁醇连续灌胃3周,3周后改为隔日一次,共12周建立大鼠高尿酸血症模型.定期检测大鼠体质量变化;12周末自动生化仪检测血尿酸(UA)水平、外周血常规;骨髓涂片检测骨髓象;ELISA方法测定大鼠血清细胞因子白细胞介素(IL)-1β水平.取肾脏组织经PAS染色,光镜观察肾脏病理结构改变.结果 与正常对照组比较,高尿酸血症模型组大鼠体质量明显降低、血尿酸水平显著增高;外周血常规中自细胞(WBC)计数和血小板(PLT)计数显著增高、红细胞(RBC)计数明显降低;血清IL-1β水平明显增高;肾脏组织内炎性细胞浸润.与模型组比较,ASRC低剂量时升高RBC计数、降低WBC、PLT计数作用显著(P＜0.05),有效降低血清IL-1β水平(P＜0.01);ASRC高剂量可有效抑制大鼠的体质量下降、降低血尿酸水平和血清IL-1β水平(P＜0.01),肾间质仅见少量的炎性细胞浸润.结论 长期应用低剂量ASRC可有效抑制高尿酸血症大鼠外周血常规的异常改变,可能与抑制炎症反应、肾脏改变轻微有关;高剂量ASRC则更好降低血尿酸水平.提示临床应用时注意药物剂量选择.
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