别嘌醇、丙磺舒以及两者联用对马兜铃酸肝肾损害保护作用研究

Protective Effect of Allopurinol or Probenecid Alone and Their Combination against Liver and Kidney Toxicity Induced by Aristolochic Acid in Mice

目的:探讨别嘌醇(A)、丙磺舒(P)以及两者联用对马兜铃酸肝肾毒性的防治作用,并初步探讨其作用机制。方法:将雄性ICR小鼠随机分为5组:正常对照组(C组)、关木通模型组(M组)、别嘌醇组(A组)、丙磺舒组(P组)、别嘌醇+丙磺舒组(A+P组)。C组灌胃等体积饮用水,后4组灌胃给予7g·kg-1·d-1的关木通水煎剂,给药4天后停药3天,持续4周;各给药组从第3周起在给予造模药的同时灌胃给予相应药物即A(70mg·kg-1·d-1)、P(360mg·kg-1·d-1)、A(70mg·kg-1·d-1)+P(360mg·kg-1·d-1)。实验结束时,测定小鼠血清肌酐(Cr)、尿素氮(BUN)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,并记录左肾、左睾系数。结果:与M组相比,各给药组均能显著降低血清Cr、BUN、ALT、AST水平,其中A+P组各指标改善作用最为显著。结论:A和P对马兜铃酸所致肝肾损伤都具有保护作用,且两药联用的效果优于两药单独应用。

Objective ： To observe the protective effect of allopurinol or probenecid alone and their combination against liver and kid- ney toxicity induced by aristolochic acid in mice, and to explore the related mechanisms preliminarily. Methods ： Male ICR mice were randomly divided into 5 groups including control （C） group, model （M） group, allopurinol （A） group, probenecid （P） group and al- lopurinol＋ probenecid （A＋P） group. The mice in control group and the other groups were given distilled water and Caulis Aristolo- chiae Manshuriensis （7g. kg -1. d -1 , the first four days per week and lasting for four weeks）. Two weeks later, A group, P group and A＋P group were treated with intragastric administration of A 70mg · kg-1 · d-1 , P 360mg · kg · -1 d -1 , A 70mg · kg -1 d -1＋P 360mg · kg · d -1 respectively besides Caulis Aristolochiae Manshuriensis. At the end of the experiment, the contents of crea- tine （Cr）, urea nitrogen （BUN）, alanine transaminase （ALT） and aspartate aminotransferase （AST） in blood serum were deter- mined. The kidney and testis coefficient were recorded as well. Results：Compared with M group, the contents of serum Cr, BUN, AI.T, AST of mice in A group, P group and A＋P group were all significantly reduced. The biochemical indicators of mice in A4-P group were improved the most significantly. Conclusion：Both allopurinol and probenecid have protective effect against the damage to liver and kidney induced by aristolochie acid and the combination therapy is prior to single therapy.