汉防己甲素降低大鼠血尿酸水平的机制研究

目的 探讨汉防己甲素对高尿酸血症大鼠血尿酸（uric acid，UA）的影响。方法 将40只SPF级别雄性大鼠按照随机数字表法分成空白对照组、高尿酸血症模型组、别嘌醇模型组、汉防己甲素低剂量模型组和汉防己甲素高剂量模型组，每组8只。用腺嘌呤（200mg/kg）与氧嗪酸钾（250mg/kg）联合饲喂酵母饲料（10g/kg）的方法构建高尿酸血症的大鼠模型，空白对照组喂普通饲料。造模成功后，从第8天起，每天下午给予别嘌呤模型组大鼠灌胃别嘌呤醇（40mg/kg），汉防己甲素低剂量模型组、汉防己甲素高剂量模型组分别灌胃16mg/kg和32mg/kg汉防己甲素，空白对照组与高尿酸血症模型组灌胃同等体积的生理盐水。给药后每周采集大鼠血液检测UA、血肌酐（serum creatinine，Scr）及血尿素氮（blood uric nitrogen，BUN）水平，处死后取肝脏检测黄嘌呤氧化酶（xanthine oxidase，XOD）和腺苷脱氨酶（adenosine deaminase，ADA）活性。结果 干预1周时，除空白对照组外，各组UA水平均显著升高（P<0.05），造模成功。与高尿酸血症模型组相比，干预2周、3周、4周时，低剂量汉防己甲素组的UA、Scr和BUN水平差异均无统计学意义（P>0.05）；干预4周时，高剂量汉防己甲素模型组的UA水平显著降低（P<0.05）。干预3周、4周时，高剂量汉防己甲素模型组Scr水平均显著降低（P<0.05），干预2周时，高剂量汉防己甲素模型组的BUN水平显著降低（P<0.05）。与高尿酸血症模型组相比，高剂量汉防己甲素模型组XOD活性显著降低（P<0.05），低剂量汉防己甲素模型组、高剂量汉防己甲素模型组ADA活性均显著降低，差异无统计学意义（P>0.05）。结论 汉防己甲素对高尿酸血症大鼠有改善效果，可能的机制是其对黄嘌呤氧化酶活性的抑制，但其具体作用机制有待进一步研究。

Study on the mechanism of tetrandrine to reduce blood uric acid level in rats

Objective To study the effect of tetrandrine on serum uric acid (UA) in hyperuricemia rats. Methods A total of 40 SPF-rated male rats were divided into blank control group, hyperuricemia model group, hyperuricemia model with allopurinol group, hyperuricemia model with tetrandrine low-dose group and hyperuricemia model with tetrandrine high-dose group according to random number table method, with 8 rats in each group. The rat model of hyperuricemia was constructed by feeding adenine (200mg/kg) with potassium oxyzincate (250mg/kg) in combination with yeast diet (10g/kg), while the blank control group was fed with normal diet. From day 8 onwards, the rats were given allopurinol (40mg/kg) by gavage in the afternoon every day, 16mg/kg and 32mg/kg of tetrandrine in the low-dose model group and high-dose model group respectively, and the same volume of saline in the blank control group as in the hyperuricemia model. After administration, blood was collected weekly from the rats to test the levels of blood UA, serum creatinine (Scr) and blood urea nitrogen (BUN), and liver was taken after execution to test the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA). Results After 1 week of intervention, UA levels were significantly higher in all groups except the blank control group (P<0.05), and modelling was successful. There was no statistically significant difference in UA, Scr and BUN levels in the hyperuricemia model with tetrandrine low-dose group at 2 weeks, 3 weeks and 4 weeks of intervention compared to the hyperuricemia model group (P>0.05). At 4 weeks of intervention, UA levels were significantly lower in the hyperuricemia model with tetrandrine high-dose group (P<0.05). At 3 and 4 weeks of intervention, the Scr level was significantly lower in the hyperuricemia model with tetrandrine high-dose group (P<0.05). At 2 weeks of intervention, BUN levels were significantly lower in the hyperuricemia model with tetrandrine high-dose group (P<0.05). XOD activity was significantly lower in the hyperuricemia model with tetrandrine high-dose group compared to the hyperuricemia model group (P<0.05). The ADA activity was significantly reduced in the hyperuricemia model with tetrandrine low-dose group and the hyperuricemia model with tetrandrine high-dose group, and the differences were not statistically significant (P>0.05). Conclusion The ameliorative effect of tetrandrine on hyperuricemia rats. The possible mechanism for the improvement of hyperuricemia in rats is the inhibition of xanthine oxidase activity, but the exact mechanism of action needs to be further investigated.