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目的 :研究糖尿病情况下肝功能的变化及对磺胺嘧啶药物代谢的影响。方法 :建立四氧嘧啶糖尿病小鼠模型 ,测定血清及肝匀浆中ALT ,GST活性、肝微粒体中细胞色素P450 、苯胺羟化酶、脱甲基酶活性 ,并测定静脉注射磺胺嘧啶 4 0 0mg·kg-1在糖尿病小鼠体内药代动力学参数。结果 :糖尿病小鼠血清中GST活性明显升高 ,肝匀浆中GST活性明显下降 ,ALT活性无明显改变 ,肝微粒体中苯胺羟化酶活性明显升高 ,对细胞色素P450 及脱甲基酶活性无明显影响。磺胺嘧啶在糖尿病小鼠体内过程符合二房室模型 ,t1/ 2 β为 (2 3 6± 4 5 4 )h ,与正常鼠相比有明显差异。结论 :糖尿病情况下GST活性改变较ALT敏感 ,对肝药酶的影响各不相同 ,因此糖尿病如何影响药物代谢取决于药物在体内的代谢方式。
Objective: To study the changes of liver function and the effects on the metabolism of sulfadiazine in patients with diabetes mellitus. Methods: Alloxan diabetic mice model was established. The activity of ALT and GST in serum and liver homogenate, the activities of cytochrome P450, aniline hydroxylase and demethylase in liver microsome were determined. The levels of sulfadiazine 4 0 Pharmacokinetic parameters of 0 mg · kg-1 in diabetic mice. Results: The serum GST activity in diabetic mice was significantly increased, the activity of GST in liver homogenate was significantly decreased, the activity of ALT was not changed and the activity of aniline hydroxylase in liver microsome was significantly increased. The cytochrome P450 and demethylase No significant effect on activity. Sulfadiazine in diabetic mice in line with the process of two-compartment model, t1 / 2 β was (23 6 ± 4 5 4) h, compared with normal rats were significantly different. CONCLUSIONS: Changes in GST activity are more sensitive to ALT than to ALT in diabetic conditions and have different effects on hepatic enzymes, so how diabetes affects drug metabolism depends on how the drug is metabolized in the body.