Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes

Han LI; Guang-ping ZHANG; Meng MA; Ping SU; Yi-fei YANG; Teng-fei CHEN; Zu-guang YE

doi:10.13422/j.cnki.syfjx.20192026

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Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes

Compatibility | 更新时间：2021-02-09

- Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 1, Pages: 59-64(2020)
- 作者机构：
  
  中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192026
  CLC： R22; R242; R2-031; R285.5
- Received：13 March 2019，
  
  Published Online：28 June 2019，
  
  Published：05 January 2020
- 稿件说明：
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Han LI, Guang-ping ZHANG, Meng MA, et al. Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 59-64.
DOI：

Han LI, Guang-ping ZHANG, Meng MA, et al. Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(1): 59-64. DOI： 10.13422/j.cnki.syfjx.20192026.

摘要

目的：

基于心脏细胞色素P450(cytochrome P450，CYP450)系统考察附子与甘草配伍后对正常大鼠心脏的减毒机制研究。

方法：

雄性SD大鼠，随机分为空白组、诱导剂苯巴比妥组(0.08 g·kg

-1

·d

-1

)，附子组(0.5 g·kg

-1

·d

-1

)，甘草组(0.5 g·kg

-1

·d

-1

)和附子-甘草组(0.5 g·kg

-1

·d

-1

)。检测大鼠心肌酶天冬氨酸氨基转移酶(aspartate transaminase，AST)，肌酸激酶(creatine kinase，CK)和乳酸脱氢酶(lactate dehydrogenase，LDH)含量变化，同时观察大鼠心脏组织的病理学改变，并观察各组对药物代谢酶CYP2B1，CYP2C11，CYP2E1，CYP2J3，CYP4A1，CYP4A3，CYP4F1，CYP4F5，CYP4F6 mRNA表达水平的变化。

结果：

与空白组比较，附子组中大鼠血清AST，CK和LDH含量升高(

0.05)，配伍后AST，CK和LDH心肌酶的含量较附子组降低，但未出现统计学差异；同时病理学结果显示附子组大鼠出现心脏损伤，配伍后甘草可减轻由附子产生的心脏损伤作用；在基因转录水平，甘草组能不同程度地上调CYP2C11和CYP2J3 mRNA表达(

0.05)，甘草与附子配伍后能上调CYP2B1，CYP2C11和CYP2J3家族mRNA表达(

0.05)，推测配伍可促进花生四烯酸(arachidonic acid，AA)代谢生成环氧二十碳三烯酸(expxyeicosatrienoic acid，EETs)，附子能上调CYP4家族中CYP4A1，CYP4A3，CYP4F1，CYP4F5和CYP4F6 mRNA表达(

0.05)，其能促进20-羟-二十烷四烯酸(20-hydroxyeicosatetraenoicacid，20-HETE)的生成，附子-甘草配伍后能削弱附子下调CYP4A3，CYP4F1，CYP4F5和CYP4F6家族mRNA表达的能力(

0.05)，抑制20-HETE的生成，减轻由附子产生的心脏毒性。

结论：

附子-甘草配伍后可调控心脏CYP450酶的表达，使EETs生成量增加，20-HETE含量减少，起到减毒的作用。

Abstract

Objective:

To investigate the effect of Aconiti Lateralis Praeparata Radix combined with Glycyrrhizae Radix et Rhizoma on mRNA expression of cytochrome P450 (CYP450) enzymes in rat' s heart.

Method:

Male Sprague Dawley rats were randomly divided into the control group

the inducer group (0.08 g·kg

-1

·d

-1

)

the aconite group (0.5 g·kg

-1

·d

-1

)

the licorice group (0.5 g·kg

-1

·d

-1

) and the compatibility group (aconite and licorice group 0.5 g·kg

-1

·d

-1

)

with 6 rats in each group. In each group

the serum concentrations of aspartate transaminase (AST)

creatine kinase (CK) andlactate dehydrogenase (LDH) were respectively measured. Hematoxylin-eosin(HE) staining was used to detect the pathologic changes in the heart tissue of the rats. The expression of several CYP genes were measured.

Result:

After combination

the contents of AST

CK and LDH were lower than those of the aconite group. At the same time

the pathological results showed cardiac injury in rats in the aconite group

and licorice could alleviate the cardiac injury caused by aconite. At the level of gene transcription

the glycyrrhizae group could up-regulate the expressions of CYP2C11 and CYP2J3 to different degrees (

0.05)

and the combination of licorice and aconite could up-regulate the expression of CYP2B1

CYP2C11 and CYP2J3 family (

0.05). It suggested that the combination could promote the formation of EETs in arachidonic acid(AA) metabolism

and the aconite could up-regulate the expressions of CYP4A1

CYP4A3

CYP4F5 and CYP4F6 in CYP4 family (

0.05)

promote the formation of 20-hydroxyeicosatetraenoic acid(20-HETE). The combination of aconite and licorice can weaken the ability of aconite

down-regulate the expression of CYP4A3

CYP4F1

CYP4F5 and CYP4F6 family mRNA (

0.05)

inhibit the formation of 20-HETE and reduce the cardiotoxicity caused by aconite.

Conclusion:

The combination of licorice and aconite can regulate the expression of CYP450 enzyme in the heart

increase the production of EETs and the content of 20-HETE

and finally play a role in reducing toxicity.

关键词

Keywords

references

唐梅，赵立春，徐敏，等．附子化学成分和药理作用研究进展 [J]．广西植物， 2017 ， 37 ( 12 )： 1614 - 1627 .

谢晓芳，彭成．附子心脏毒效的多维评价和整合分析研究进展 [J]．世界中医药， 2017 ， 12 ( 11 ): 2555 - 2562 .

国家药典委员会．中华人民共和国药典：一部 [M]．北京：中国医药科技出版社， 2015 ： 86 - 87，191-193 .

K Peter ， J Schinnerl ， S Felsinger ， et al . A novel concept for detoxification: complexation between aconitine and liquiritin in a Chinese herbal formula ('Sini Tang') [J]. J Ethnopharmacol ， 2013 ， 149 ( 2 )： 562 - 569 .

Y Y ZHANG ， L YU ， W F JIN ， et al . Reducing toxicity and increasing efficiency: aconitine with liquiritin and glycyrrhetinic acid regulate calcium regulatory proteins in rat myocardial cell [J]. Afr J Tradit Complem ， 2017 ， 14 ( 4 )： 69 - 79 .

李文，杨晓琴，章津铭，等 . 附子配伍甘草后对附子生物碱类成分大鼠在体肠吸收特性的影响 [J]. 中国实验方剂学杂志， 2018 ， 24 ( 22 )： 11 - 16 .

马增春，周思思，梁乾德，等．基于UPLC-TOF/MS分析人参附子配伍减毒的物质基础 [J]．药学学报， 2011 ， 46 ( 12 )： 1488 - 1492 .

李晗，王宇光，马增春，等．基于临床用量的参附注射液对大鼠肝脏主要药物代谢酶的影响 [J]．药学学报， 2013 ， 48 ( 5 )： 728 - 733 .

蔡悦，梁红玉，王建立，等．甘草附子汤对佐剂性关节炎小鼠的治疗作用 [J]．中国实验方剂学杂志， 2018 ， 24 ( 14 )： 142 - 146 .

沈红，朱玲英，姚楠，等．甘草与附子配伍对乌头碱、新乌头碱、次乌头碱大鼠药动学的影响 [J]．中药材， 2011 ， 34 ( 6 )： 937 - 942 .

R J Roman . P-450 metabolites of arachidonic acid，in the control of cardiovascular function [J]. Physiol Rev , 2002 ， 82 ( 1 )： 131 - 185 .

R H Elbekai , A O S ElKadi . Cytochrome P450 enzymes: central players in cardiovascular health and disease [J]. Pharmacol Ther ， 2006 ， 112 ( 2 )： 564 - 587 .

A ElKadi ， B Zordoky . Modulation of cardiac and hepatic cytochrome P450 enzymes during heart failure [J]. Curr Drug Metab ， 2008 ， 9 ( 2 )： 122 - 128 .

张广平，朱丽君，周娟，等．附子配伍甘草对CYP3A4体内活性的影响研究 [J]．中国中药杂志， 2012 , 37 ( 15 )： 2206 - 2209 .

郭丽丽，唐雪春．《伤寒论》、《金匮要略方论》中附子应用特点的文献研究 [J]．新中医， 2011 ， 43 ( 11 )： 108 - 109 .

覃琴，冯柏林，唐丽清，等 . 五加科植物中药对胆固醇的调节作用及机制研究进展 [J]. 中国实验方剂学杂志， 2019 ， 25 ( 10 )： 197 - 204 .

P J O' Brien ， D E C Smith , T J Knechtel ， et al . Cardiac troponin I is a sensitive，specific biomarker of cardiac injury in laboratory animals [J]. Lab Anim Sci , 2006 , 40 ( 2 ): 153 - 171 .

D B Walker . Serum chemical biomarkers of cardiac injury for nonclinical safety testing [J]. Toxicol Pathol , 2006 ， 34 ( 1 )： 94 - 104 .

L CHEN ， R Ackerman ， M Saleh ， et al . 20-HETE regulates the angiogenic functions of human endothelial progenitor cells and contributes to angiogenesis in vivo [J]. J Pharmacol Exp Ther ， 2014 ， 348 ( 3 )： 442 - 451 .

彭秋菊，严华成，石磊 . 细胞色素P450 SNP与冠心病易感性关系的研究进展 [J]．中国临床药理学与治疗学， 2018 ， 23 ( 4 )： 477 - 480 .

J M Lasker , W B CHEN ， I Wolf ， et al . Formation of 20-hydroxyeicosatetraenoic acid，a vasoactive and natriuretic eicosanoid，in human kidney. Role of Cyp4F2 and Cyp4A11 [J]. J Biol Chem ， 2000 ， 275 ( 6 )： 4118 - 26 .

Z FU ， Y MA ， X XIE ， et al . A novel polymorphism of the CYP4A11 gene is associated with coronary artery disease .[J]. Clin Appl Thromb Hemost ， 2013 ， 19 ( 1 )： 60 - 65 .

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