长期服用别嘌醇片与别嘌醇缓释微丸胶囊对高尿酸血症大鼠肝脏作用的对比实验研究

The effects of allopurinol sustained-release capsules on liver in experimental hyperuricacidemia rats by long time administration

目的考察长期(3个月)应用别嘌醇缓释微丸胶囊(奥迈必利)对高尿酸血症大鼠肝脏功能和组织结构的影响。方法试验大鼠分为正常对照组、高尿酸血症模型组、别嘌醇缓释微丸胶囊治疗组(低、高剂量)、别嘌醇片治疗组(低、高剂量)。除正常对照组以外,其余各组采用腺嘌呤和乙胺丁醇连续灌胃3周,3周后改为隔日1次的方法,共3个月造成大鼠持续性高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释微丸胶囊或别嘌醇片,在实验3个月末,检测大鼠血尿酸含量、肝脏病理结构、反映肝功能的主要酶(丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶)的活性和肝脏指数(%)的改变。结果与正常对照组比较,高尿酸痛风模型大鼠血尿酸水平显著增高(P<0.05);天冬氨酸转氨酶活性显著增高、碱性磷酸酶活性显著降低(P<0.05);肝脏指数增高、肝脏组织结构发生病理改变。与高尿酸血症模型大鼠比较,长时间服用别嘌醇缓释微丸胶囊和别嘌醇片均可降低高尿酸血症大鼠血尿酸水平,缓解高尿酸大鼠的肝脏组织结构损伤,其中别嘌醇缓释微丸胶囊高剂量时作用显著(P<0.05);别嘌醇缓释微丸胶囊和别嘌醇片均可降低高尿酸血症大鼠天冬氨酸转氨酶活性、增高碱性磷酸酶活性,其中别嘌醇缓释微丸胶囊高剂量时升高碱性磷酸酶的作用显著(P<0.05);别嘌醇缓释微丸胶囊和别嘌醇片均可降低痛风大鼠肝脏指数,其中别嘌醇缓释微丸胶囊低剂量时作用显著(P<0.05)。结论长期应用别嘌醇缓释微丸胶囊(奥迈必利)可有效降低高尿酸血症大鼠的血尿酸水平、改善肝脏功能,保护肝脏组织结构,其作用优于相当剂量的别嘌醇片。

Objective To detect the effects of allopurinol sustained-release capsules（ASRC） on liver in experimental hyperuricacidemia rats by long time administration（3 months）.Methods We first divided Wistar rats into 6 subgroups： normal group,hyperuricacidemia rat model group,ASRC treatment groups（low and high dose） and allopurinol tablet treatment groups（low and high dose）.Except for the rats of normal group,we make other groups of rats to constant hyperuricacidemia rate with adenine and ethambutol hydrochloride by continual intragastric（i.g） administration for 3 weeks and changing to administration every two day till 3 months.At the same time,we treated these rats with two doses of allopurinol sustained-release capsules（low and high）,as well as two doses of allopurinol tablets as control.After that,we detected the content of serum uric acid,a parameters reflecting liver function.Results Adenine and Ethambutol hydrochloride increase the content of serum uric acid in rats.The activity of AST increased,but the activity of ALP decreased.Furthermore,the liver index obviously increased,and tissue structures of liver have pathological changes in hyperuricacidemia rat.In comparison,long-term taking ASRC can decrease the level of serum uric acid in hyperuricacidemia rats and the effect was more obvious by high dose administration.ASRC can reduce the activity of AST,but increase that of ALP in hyperuricacidemia rats.The effect of increasing activity of ALP was obvious when taking high dose of ASRC.Furthermore,ASRC decreased liver index of hyperuricacidemia rat,which is more obvious by low dose administration.ASRC also reduced the degree of histopathological damage of liver.Conclusion Compared to corresponding dose of allopurinol tablets,long-term taking the ASRC can obviously decrease the level of serum uric acid,improve the function of liver,and protect the tissue structure of liver in hyperuricacidemia rats.