复方丹参滴丸对大鼠肝CYP_(450)酶系诱导作用的研究

Study on Rat Liver Cytochrome P_(450) Induction Effect of Compound Danshen Dripping Pills

目的 观察复方丹参滴丸诱导处理对大鼠肝细胞色素P450 及其主要亚型的影响。方法 Wistar大鼠用 1 2 5、75 0、45 0 0mg·kg-1 ·d-1 复方丹参滴丸连续灌胃诱导处理 5d ,测定微粒体中总CYP450 含量和CYP1A2、2B1 / 2、2E1和 3A亚型活性。结果 不同剂量复方丹参滴丸诱导处理后大鼠肝脏脏器系数、总CYP450 含量及CYP1A2、2E1、3A亚型活性未见明显增高。高剂量复方丹参滴丸诱导后 ,大鼠肝脏CYP2B1 / 2活性与空白对照组相比有显著升高 (P <0 .0 5 ) ,中、低剂量组CYP2B1 / 2活性未见明显升高。相应的阳性对照剂均导致肝脏CYP450 及其亚型活性明显升高。结论 复方丹参滴丸对大鼠肝脏CYP450 及主要亚型CYP1A2、2E1、3A无诱导效应 ,高剂量下仅对CYP2B1 / 2有轻度诱导效应 ,此种作用无明显临床意义。

Aim To observe the induction effect of Compound Danshen Dripping Pills on rat cytochrome P 450 and its main subtypes.Methods Compound Danshen Dripping Pills was administered at 125,750,4 500mg·kg -1 ·d -1 to male Wistars rats by stomach tube(ig) for five days.Then total cytochrome P 450 contents of microsome and activities of P 450 subtypes CYP1A2,2B1/2,2E1,3A in liver tissue were detected.Results The liver/body weight ratios,total CYP 450 contents and activities of CYP1A2,2E1,3A in Compound Danshen Dripping Pills treated groups at different doses didn't change significantly compared with those of the negative control group.Activities of CYP2B1/2 in liver microsome increased significantly only in high dose group(P<0.05,compared with that of the negative control group).Total CYP 450 contents and the activities of the four subtypes mentioned above were increased to different degrees in the four positive control groups,respectively.Conclusion Total CYP 450 contents and activities of its main subtypes CYP1A2, 2E1,3A in rat liver tissue couldn't be induced by Compound Danshen Dripping Pills,only activity of CYP2B1/2 was slightly induced by Compound Danshen Dripping Pills at high dose(4 500mg·kg -1 ·d -1 ,360 times as high as the dose used in clinic). This effect didn't have any clinical significance.