健脾和胃方对大鼠肝微粒体CYP3A1酶活性的影响

目的研究健脾和胃方对大鼠肝微粒体细胞色素P450同工酶3A1（CYP3A1）活性的作用。方法 25只大鼠随机分为5组：空白对照组（生理盐水1 mL·kg-1·d-1,14 d）、地塞米松组（100 mg·kg-1·d-1,3 d）和健脾和胃方高、中、低剂量组（7.146,3.573,1.786 mg·kg-1·d-1,14 d）,每组5只,灌胃给予相应的药物。采用高效液相色谱-紫外检测法,以睾酮为探针,测定睾酮经大鼠肝微粒体温孵后转化的代谢产物6β-羟基睾酮（6β-OHT）的生成速率,以评价各组CYP3A1酶活性。结果空白对照组、地塞米松组和健脾和胃方高、中、低剂量组6β-OHT的生成速率分别为（7.29±0.66）、（27.46±2.35）、（3.51±0.48）、（4.90±1.18）、（6.52±1.23）nmol·mg-1·min-1,健脾和胃方高、中、低剂量组6β-OHT的生成速率与地塞米松组均有显著性差异（P〈0.05）。高、中剂量组与空白对照组有显著性差异（P〈0.05）,低剂量组与空白对照组无显著性差异（P〉0.05）。结论本实验结果表明健脾和胃方对大鼠肝药酶CYP3A1酶活性无诱导作用,健脾和胃方的高、中剂量组能使大鼠肝药酶CYP3A1酶活性下降。

Effects of Jianpiheweifang on Enzymic,Activity of CYP3A1 in Liver Microsome of Rats

Objective To study the effect of Jianpiheweifang on the enzymic activity of liver microsomal cytochrome P450 isoenzyme 3A1 （CYP 3A1） in SD rats.Methods A total of 25 SD rats were randomly divided into 5 groups： blank control group （NS, 1 mL· kg-l · d-1, 14 d）, dexamethasone group （100 mg · kg-1 · d-l）, Jianpiheweifang high-dose, medium-dose and low-dose groups （7.146, 3.573, 1.786 mg ·kg-1·d-1）, with 5 rats in each group. Those groups were given relevant medicine intragastrically. The HPLC-UV method was established and validated to determine the productive velocity of metabolite （63-hydroxyl-testosterone, 6β-OHT） of testosterone after incubation of rat liver microsome and to measure the activity of CYP3A1. Results The productive velocities of 6β-OHT in rats of the blank control group, dexamethasone group and Jianpiheweifang high-dose, medium-dose and low-dose groups were （7.29±0.66） , （27.46± 2.35）, （3.51±0.48）, （4.90±1.18） and （6.52±1.23） nmol · mg-1· min-1, respectively. There were significant differences between Jianpiheweifang groups and dexamethasone group （P 〈 0.05 ）. There were significant differences between the high-dose, medium-dose group and the blank control group （P〈0.05） , but there was no significant difference between low-dose group and the blank control group （P〉0.05）.Conclusion Jianpiheweifang had no inducible effect on the enzymic activity of CYP3A1 in rats. The high-dose, medium-dose of Jianpiheweifang can reduce the activity of CYP3A1 in rats.