[1]俸 珊,俸 娜,付玉颖,等.对乙酰氨基酚对不同妊娠期小鼠肝肾功能的影响及机制研究[J].中国药理学通报,2018,(08):1120-1125.[doi:10.3969/j.issn.1001-1978.2018.08.018]
 FENG Shan,FENG Na,FU Yu-ying,et al.Effects of APAP on liver and kidney function in different pregnancy stage and related mechanism[J].Chinese Pharmacological Bulletin,2018,(08):1120-1125.[doi:10.3969/j.issn.1001-1978.2018.08.018]
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对乙酰氨基酚对不同妊娠期小鼠肝肾功能的影响及机制研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1120-1125
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
Effects of APAP on liver and kidney function in different pregnancy stage and related mechanism
文章编号:
1001-1978(2018)08-1120-06
作者:
俸 珊1俸 娜2付玉颖1邹 利1刘 珂1任 巧1徐晓玉1
1.西南大学药学院,重庆 400715; 2.成都市青白江区人民医院重症监护病房,四川 成都 610300
Author(s):
FENG Shan1 FENG Na2 FU Yu-ying1 ZOU Li1 LIU Ke1 REN Qiao1 XU Xiao-yu1
1.College of Pharmacy, Southwest University, Chongqing 400715, China; 2.ICU, Qing baijiang Hospital of Chengdu, Chengdu 610300,China
关键词:
对乙酰氨基酚 孕鼠 肝毒性 CYP450s N-乙酰-对苯醌亚胺 GSH
Keywords:
acetaminophen pregnant mice hepatotoxicity CYP450s NAPQI GSH
分类号:
R-332; R322.47; R345.99; R575.022; R714.1; R971.1; R977.3
DOI:
10.3969/j.issn.1001-1978.2018.08.018
文献标志码:
A
摘要:
目的 研究对乙酰氨基酚(acetaminophen, APAP)对不同妊娠期小鼠肝肾功能的影响及其机制。方法 分别给予未妊娠、妊娠中期和晚期小鼠500 mg·kg-1 APAP(文献报道最大可耐受剂量)后,于0、6、24、48 h取材,全自动生化仪测定肝脏和肾脏的血液生化指标; LC-MS/MS的cocktail探针法测定CYP450s代谢酶活性; HE染色法观察肝、肾组织病理学变化; LC-MS/MS法测定APAP活性代谢产物N-乙酰-对苯醌亚胺(NAPQI)-GSH结合物。结果 小鼠肝CYP450s活性在妊娠中期上调,而在妊娠晚期恢复到正常水平; 小鼠肝SOD活性在妊娠中期和晚期均上调,而肝脏GSH水平仅在妊娠中期明显高于未妊娠组。APAP可致妊娠中期小鼠产生轻微肝损伤,主要表现为ALT、AST、ALP、MDA 水平升高(P<0.05),而SOD和GSH 含量降低,同时其肝脏中的NAPQI-GSH水平明显升高(P<0.05)。APAP对未妊娠和妊娠晚期小鼠肝功能影响较小,APAP对妊娠各期小鼠肾功能无明显影响。结论 500 mg·kg-1 APAP仅致妊娠中期小鼠产生急性轻微肝损伤,这可能与妊娠中期小鼠肝CYP450s活性升高,但同时伴随肝SOD活性和GSH水平升高有关。
Abstract:
Aim To observe the effects of acetaminophen(APAP)on liver and kidney function in mice with different gestational ages.Methods 500 mg·kg-1 APAP was given to non-preganancy, middle preganancy and late-pregnancy mice by oral administration, then they were sacrificed at 0, 6, 24 and 48 h.The changes of alanine aminotransferase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine and antioxidation indices superoxide dismutase(SOD), malonic dialdehyde(MDA), glutathione(GSH)and liver, kidney histological evaluation were determined.The activity of liver CYP450s and contents of liver NAPQI were detected by LC-MS/MS method.Results 500 mg·kg-1 APAP only caused mild liver injury in mice with mid-pregnancy as reflected by the increased of ALT, AST and ALP levels.Besides, the CYP450s activity, SOD activity and GSH contents were significantly up-regulated in mid-pregnancy mice.What's more, 500 mg·kg-1 APAP has less effect on non-preganancy and late-preganancy mice liver function.Also, no effect was observed on the mice kidney function in all groups.Conclusion In conclusion, 500 mg·kg-1 APAP can induce mild acute liver injury in mice during the mid-pregnancy, which may be explained by the increase of CYP450s activity, SOD activity and GSH contents.

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备注/Memo

备注/Memo:
收稿日期:2018-03-17,修回日期:2018-04-22
基金项目: 西南大学基本科研业务费(No XDJK2015C155); 西南大学博士基金资助项目(No SWU114055); 重庆市基础科学与前沿技术研究项目(No cstc2017jcyjAX0137); 国家自然科学基金面上项目(No 81572678)
作者简介:俸 珊(1986-),女,博士,讲师,研究方向:中药代谢及肝毒性,E-mail:fengshan@swu.edu.cn;
徐晓玉(1958-),女,硕士,教授,研究方向:中药药理学及新药研发,通讯作者,Tel:023-68250765,E-mail:xuxiaoyu@swu.edu.cn
更新日期/Last Update: 2018-07-26