双酪氨酸灌胃对小鼠心肌功能和能量代谢的影响
首发时间：2018-01-23
摘要：目的：探究摄入酪氨酸氧化产物及其主要成分双酪氨酸对小鼠心肌功能和能量代谢的影响。方法：30只健康雌性昆明小鼠，随机分成3组：正常组（Con），每天灌胃无菌生理盐水；氧化酪氨酸组（O-Tyr）和双酪氨酸组（Dityr），每天分别灌胃剂量为320 μg/kg体质量的酪氨酸氧化产物和双酪氨酸。连续灌胃10周之后取样，进行指标测定。结果：与对照组相比，O-Tyr和Dityr灌胃显著增加了小鼠血浆和心肌中蛋白质氧化产物和脂质过氧化物（DT、AOPPs、3-NT、MDA）的含量（P<0.05），降低了血浆和心肌抗氧化能力（T-AOC、GSH/GSSG）（P<0.05），增加了血浆CK、CK-MB、cTnI、LDH的水平（P<0.05），增加了血浆和心肌中FFA的含量（P<0.05），降低了心肌Na+-K+ ATP酶、Ca2+-ATP酶、LDH的活性（P<0.05），增加了血浆CRP和TNF-α的含量（P<0.05），上调了心肌炎症因子相关基因NF-κB、TNF-α、IL-6、IL-1β mRNA的表达水平（P<0.05），对小鼠心肌能量代谢基因表达（AMPK、PPARα、CPT-I、PFK1、CS、ogdh等）造成影响。结论：酪氨酸氧化产物和双酪氨酸会引起小鼠机体氧化应激反应，心肌蛋白质和脂质氧化产物累积；造成心肌组织损伤和炎症反应; 导致心肌能量代谢障碍，影响心肌功能。双酪氨酸，作为酪氨酸氧化产物的主要成分，可能在酪氨酸氧化产物引起小鼠心肌损伤的过程中起着主要作用。
关键词： 氧化酪氨酸 双酪氨酸 氧化应激 能量代谢 心肌功能
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Effects of Dityrosine Administration on Myocardial Function and Energy Metabolism in Mice
Abstract：Objective: To study the effects of oxidized tyrosine products and dityrosine on myocardial function and energy metabolism in 10-week-gavaged mice. Methods: 30 Female Kunming mice were assigned to three groups: gavaged with saline (Con), oxidized tyrosine products (O-Tyr) and dityrosine (Dityr) for 320 μg/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 LDH), the activities of Na+-K+ ATPase, Ca2+-ATPase, LDH in myocardium, level of FFA, markers of inflammatory factor (CRP and TNF-α) in mice plasma and myocardium were investigated and the genes related to inflammatory response and energy metabolism 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) in mice plasma and myocardium, 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), lactate dehydrogenase (LDH) in plasma , increased the levels of free fatty acids(FFA) in plasma and myocardium, and decreased the activities of Na+-K+ ATPase, Ca2+-ATPase, LDH 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. The gene expression of energy metabolism were shifted(AMPK, PPARα, CPT-I, PFK1, CS, ogdh.etc). Conclusion: Our findings reveal that 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. O-Tyr and Dityr lead to myocardial energy metabolism disorders, affecting myocardial function. 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. in mice plasma.
Keywords： oxidized tyrosine dityrosine oxidative stress energy metabolism myocardial function
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