[1]王 涛,林 琴,刘凤婷,等.IL-1、TNF-α在免疫性肝损伤过程中对代谢酶CYP2E1的调控作用[J].中国药理学通报,2019,(08):1160-1164.[doi:10.3969/j.issn.1001-1978.2019.08.024]
 WANG Tao,LIN Qin,LIU Feng-ting,et al.Regulation of IL-1 and TNF-α on metabolic enzyme CYP2E1 in immunological liver injury in rats[J].Chinese Pharmacological Bulletin,2019,(08):1160-1164.[doi:10.3969/j.issn.1001-1978.2019.08.024]
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IL-1、TNF-α在免疫性肝损伤过程中对代谢酶CYP2E1的调控作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1160-1164
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Regulation of IL-1 and TNF-α on metabolic enzyme CYP2E1 in immunological liver injury in rats
文章编号:
1001-1978(2019)08-1160-05
作者:
王 涛林 琴刘凤婷李晓霞薛永志
包头医学院药物代谢与肝脏分子药理研究所,药理学教研室,内蒙古 包头 014060
Author(s):
WANG Tao LIN Qin LIU Feng-ting LI Xiao-xia XUE Yong-zhi
Institute of Pharmacolinetics and Liver Molecular Pharmacology, Dept of Pharmacology, Baotou Medical College, Baotou Inner Mongolia 014060, China
关键词:
肝损伤 核转录因子κB 吡咯烷二硫氨基甲酸 细胞色素P450 2E1 细胞色素P450 卡介苗
Keywords:
liver injury NF-κB ammonium pyrrolidinedithiocarbamate cytochrome P450 2E1 cytochrome P450 Bacillus Calmette-Guérin
分类号:
R-332; R322.47; R392.12; R345.99; R575; R593; R977.3; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.08.024
文献标志码:
A
摘要:
目的 探讨在免疫性肝损伤过程中,炎性细胞因子白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)对药物代谢酶细胞色素P450 2E1(cytochrome P450 2E1,CYP2E1)的调控作用及其机制。方法 采用尾静脉注射BCG(125 mg·kg-1)制备免疫性肝损伤大鼠模型。HPLC法检测CYP2E1的探针药物氯唑沙宗在大鼠体内的血药浓度经时变化,反映其代谢活力; 采用ELISA法检测大鼠肝组织IL-1β、TNF-α的变化; 采用Western blot检测CYP2E1蛋白表达。结果 大鼠尾静脉注射BCG 14 d后,可引起肝实质及汇管区周围有大量单核细胞及淋巴细胞浸润,形成大小不等且弥漫性分布的大量肉芽肿团块,IL-1β、TNF-α高表达(P<0.01),CYP2E1代谢活力和蛋白表达明显降低(P<0.05)。CYP2E1蛋白含量与IL-1β(r=0.222,P=0.027)呈负相关。采用PDTC钝化核转录因子κB(NF-κB)活化,可抑制肝组织中IL-1β、TNF-α高表达,减缓CYP2E1代谢活力和蛋白表达的下调。结论 NF-κB可能通过调控炎性细胞因子IL-1β、TNF-α,参与CYP2E1的调控。
Abstract:
Aim To investigate the regulation and mechanism of inflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)on the drug metabolism enzyme cytochrome P450 2E1 (CYP2E1)during immune-mediated liver injury.Methods By injection of Bacillus Calmette-Guerin(BCG,125 mg·kg-1)prepared rat model of immunological liver damage.To detection of CYP2E1 probe drug chlorzoxazone in blood concentration changes of rats over time reflects its metabolic activity by high-performance liquid chromatography(HPLC)assay.The changes of IL-1β and TNF-α in liver tissue of rats were detected by ELISA.The expression of CYP2E1 protein was determined by Western blot analysis.Results After 14 days of BCG injection of rats, a large number of mononuclear cells and lymphocytes infiltrated around the liver parenchyma and the portal area, resulting in a large number of granuloma masses with different sizes and diffuse distribution,IL-1β and TNF-α high expression(P<0.01), CYP2E1 metabolic activity and protein expression were significantly decreased(P<0.05).The protein content of CYP2E1 was significantly negatively correlated with IL-1β(r=0.222, P=0.027).Activation of PDTC-mediated nuclear factor-kappa B(NF-κB)inhibited the high expression of IL-1β and TNF-α in liver tissue and slowed down the down-regulation of CYP2E1 metabolism and protein expression.Conclusions NF-κB may be involved in the regulation of CYP2E1 by regulating the inflammatory cytokines IL-1β and TNF-α.

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备注/Memo

备注/Memo:
收稿日期:2019-03-14,修回日期:2019-04-26
基金项目:国家自然科学基金资助项目(No 81460567); 内蒙古自然科学基金资助项目(No 2009MS1104, 2014MS0813); 内蒙古自治区高等学校科学研究项目(No NJ03148,NJZY13244)
作者简介:王 涛(1995-),女,硕士生,研究方向:肝脏免疫药理学,E-mail:wangtao414414@163.com;
薛永志(1968-),男,硕士,教授,硕士生导师,研究方向:药物代谢动力学,通讯作者,E-mail:xyzhxyzh68@sohu.com
更新日期/Last Update: 2019-08-14