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[二酪氨酸给药诱导小鼠心肌损伤和炎症反应]

[Dityrosine administration induces myocardium injury and inflammatory response in mice].

作者信息

Zhang Hui, Yang Yuhui, Yan Biao, Tang Xue, Cheng Xiangrong, Le Guowei, Shi Yonghui

机构信息

State Key Laboratory of Food Science & Technology, Jiangnan University, Wuxi 214122, China.

出版信息

Wei Sheng Yan Jiu. 2018 May;47(3):345-351.

PMID:30081997
Abstract

OBJECTIVE

To study the effects of oxidized tyrosine products and dityrosine on the myocardial injury and inflammatory response in 10-week-gavaged mice.

METHODS

A total of 30 female Kunming mice were assigned to three groups: gavagedwith saline( Con), oxidized tyrosine products( O-Tyr) and dityrosine( Dityr) for 320μg/kg BW for 10 weeks. Levels of oxidized protein products( DT, AOPPs, 3-NT) and lipid peroxidation products( MDA), oxidative stress( T-AOC and GSH/GSSG), markers of myocardium injury( CK, CK-MB, cTnI and Ca~(2+)-ATPase), markers of inflammatory factor( CRP and TNF-α) were investigated and the genes related to inflammatory response were detected by Real-time quantitative( PCR).

RESULTS

10 weeks of gavage experiments enhanced the levels of dityrosine( DT), advanced oxidation protein products( AOPPs), 3-nitrotyrosine( 3-NT), and malondialdehyde( MDA), and decreased total antioxidant capacity( T-AOC) and the ratio of reduced glutathione to oxidized glutathione( GSH/GSSG) in mice plasma and myocardium. Besides, O-Tyr and Dityr increased the levels of creatine kinase( CK), creatine kinase isoenzymes( CK-MB), cardiac troponin I( cTnI) in plasma anddecreased the activities of Ca~(2+)-ATPase in myocardium. O-Tyr and Dityr increased the levels of C-reactive protein( CRP) and tumour necrosis factor α( TNF-α) in plasma. The gene expression of inflammatory response were up-regulated.

CONCLUSION

O-Tyr and Dityr increase the accumulation of myocardial protein oxidation and lipid peroxidation products and induce oxidative damage to myocardium. O-Tyr and Dityr may cause myocardial tissue injury and inflammatory response. Dityrosine, as the main component of tyrosine oxidative products, may play a major role in the process of oxidized tyrosine products causing myocardial injury in mice.

摘要

目的

研究氧化酪氨酸产物和二酪氨酸对灌胃10周小鼠心肌损伤及炎症反应的影响。

方法

将30只雌性昆明小鼠分为三组:分别用生理盐水(Con)、氧化酪氨酸产物(O-Tyr)和二酪氨酸(Dityr)按320μg/kg体重灌胃10周。检测氧化蛋白产物(DT、AOPPs、3-NT)和脂质过氧化产物(MDA)水平、氧化应激(T-AOC和GSH/GSSG)、心肌损伤标志物(CK、CK-MB、cTnI和Ca²⁺-ATPase)、炎症因子标志物(CRP和TNF-α),并通过实时定量聚合酶链反应(PCR)检测炎症反应相关基因。

结果

10周灌胃实验使小鼠血浆和心肌中二酪氨酸(DT)、晚期氧化蛋白产物(AOPPs)、3-硝基酪氨酸(3-NT)及丙二醛(MDA)水平升高,总抗氧化能力(T-AOC)及还原型谷胱甘肽与氧化型谷胱甘肽比值(GSH/GSSG)降低。此外,O-Tyr和Dityr使血浆中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)水平升高,心肌中Ca²⁺-ATPase活性降低。O-Tyr和Dityr使血浆中C反应蛋白(CRP)和肿瘤坏死因子α(TNF-α)水平升高,炎症反应相关基因表达上调。

结论

O-Tyr和Dityr增加心肌蛋白氧化和脂质过氧化产物的蓄积,诱导心肌氧化损伤。O-Tyr和Dityr可能导致心肌组织损伤和炎症反应。二酪氨酸作为酪氨酸氧化产物的主要成分,可能在氧化酪氨酸产物致小鼠心肌损伤过程中起主要作用。

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