曲马多对大鼠CYP450及其肝功能的影响

黄丽娜; 陈聪; 易林高; 吴安生; 蔡啸静; 娄晓辉

doi:10.16766/j.cnki.issn.1674-4152.000489

曲马多对大鼠CYP450及其肝功能的影响

doi: 10.16766/j.cnki.issn.1674-4152.000489

瑞安市人民医院麻醉疼痛科, 浙江瑞安 325200

基金项目:

浙江省医药卫生科技计划项目(2012KYB195)；温州市科技计划项目(Y20160388)

详细信息

通讯作者:
娄晓辉,E-mail:louxiaohui@163.com

中图分类号: R971;R969.3
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出版历程
- 收稿日期: 2018-06-16
- 网络出版日期: 2022-08-06

Effect of tramadol on level of CYP450 and liver function in rats

Department of Anesthesiology and Pain Management, the People's Hospital of Rui'an City, Rui'an, Zhejiang 325200, China

摘要

摘要: 目的考察曲马多依赖性大鼠模型肝脏CYP450酶活力及肝功能指标的变化。方法将30只SD大鼠分为空白组、阳性对照组和实验组,每组10只,各组分别以生理盐水、80 mg/(kg·d)苯巴比妥和60 mg/(kg·d)曲马多灌胃给药,建立曲马多依赖性大鼠模型;采用Cocktail体外孵育法结合液质联用(LC-MS)技术测定大鼠肝脏中CYP1A2、CYP2B1、CYP2C11、CYP2D2、CYP2E1、CYP3A1各同工酶酶活性;RT-qPCR技术对上述同工酶的mRNA表达水平进行检测;血生化仪分析肝功指标。结果 ①与空白组相比,阳性对照组CYP1A2、CYP2B1、CYP2C11、CYP2E1、CYP3A1酶活性分别为(190.15±33.58)、(98.02±36.00)、(1 348.79±40.76)、(3 214.66±133.51)、(292.76±33.32)μg/ml,显著高于空白组,差异有统计学意义(P<0.05);②与空白组相比,阳性对照组CYP1A2、CYP2B1、CYP2C11、CYP2E1、CYP3A1 mRNA表达显著上调,分别上调(89.88±14.22)%、(95.12±16.00)%、(351.25±32.33)%、(556.85±42.88)%、(52.56±11.12)%,差异有统计学意义,CYP2D2 mRNA无明显变化。实验组CYP1A2、CYP2B1、CYP2E1、CYP2D2 mRNA表达分别上调(75.12±21.45)%、(66.32±18.14)%、(81.35±23.55)%、(382.74±33.25)%,差异有统计学意义,CYP2C11、CYP3A1 mRNA表达无明显变化。③在肝脏生化指标水平上,与空白组相比,阳性对照组和实验组ALT、AST、LDH含量均明显上升,差异有统计学意义。结论曲马多滥用会诱导大鼠CYP1A2、CYP2B1、CYP2E1和CYP2D2酶活性升高和肝脏损伤。
- 曲马多 /
- 滥用 /
- CYP450 /
- 肝功能
Abstract: Objective To investigate the changes of hepatic CYP450 activity and liver function in tramadol dependent rats. Methods Total 30 SD rats were divided into blank group, positive control group and experimental group, with 10 rats in each group. Each group was administered with saline, 80 mg/(kg·d) phenobarbital and 60 mg/(kg·d) tramadol. The rat model of tramadol dependent rats was established. Cocktail in vitro incubation method combined with liquid mass spectrometry (LC-MS) technology were used to test the isozymes activities of CYP1A2, CYP2B1, CYP2C11, CYP2D2, CYP2E1, CYP3A1 in rat liver were measured, and RT-qPCR technique was used to detect the level of mRNA expression of the above isozymes, and the blood biochemical analyzer was used to analyze the liver function index. Results ① Compared with the blank group, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 in the positive control group were (190.15±33.577), (98.018±36.00), (1 348.79±40.76), (3 214.66±133.51) and (292.76±33.32) μg/ml, which were significantly higher than those in the blank group (P<0.05). The difference was statistically significant. ②Compared with the blank group, the expression of CYP1A2, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 mRNA in the positive control group was significantly up, (89.88±14.22)%, (95.12±16)%, (351.25±32.33)%, (556.85±42.88)% and (52.56±11.12)%, and the difference was statistically significant, and there was no significant change in CYP2D2 mRNA. The expression of CYP1A2, CYP2B1, CYP2E1 and CYP2D2 mRNA in the experimental group was up (75.12±21.45)%, (66.32±18.14)%, (81.35±23.55)% and (382.74±33.25)%. The difference was statistically significant. There was no significant change in the expression of CYP2C11 and CYP3A1 mRNA. ③In the liver biochemical index level, compared with the blank group, the content of ALT, AST and LDH in the positive control group and the experimental group increased significantly, and the results were statistically significant. Conclusion The abuse of tramadol may induce an increased activity of CYP1A2, CYP2B1, CYP2E1 and CYP2D2 and liver injury in rats.
- Tramadol /
- Abuse /
- CYP450 /
- Liver function