Kudchodkar Bhalchandra J, Pierce Anson, Dory Ladislav
Department of Molecular Biology & Immunology, The University of North Texas Health Science Center, Fort Worth, TX 76104, USA.
Atherosclerosis. 2007 Jul;193(1):28-35. doi: 10.1016/j.atherosclerosis.2006.08.018. Epub 2006 Sep 14.
We previously demonstrated that hyperbaric oxygen (HBO) treatment inhibits diet-induced atherosclerosis in New Zealand White rabbits. In the present study we investigate the mechanisms that might be involved in the athero-protective effect of HBO treatment in a well-accepted model of atherosclerosis, the apoE knockout (KO) mouse. We examine the effects of daily HBO treatment (for 5 and 10 weeks) on the components of the anti-oxidant defense mechanism and the redox state in blood, liver and aortic tissues and compare them to those of untreated apoE KO mice. HBO treatment results in a significant reduction of aortic cholesterol content and decreased fatty streak formation. These changes are accompanied by a significant reduction of autoantibodies against oxidatively modified LDL and profound changes in the redox state of the liver and aortic tissues. A 10-week treatment significantly reduces hepatic levels of TBARS and oxidized glutathione, while significantly increases the levels of reduced glutathione, glutathione reductase (GR), transferase, Se-dependent glutathione peroxidase and catalase (CAT). The effects of HBO treatment are similar in the aortic tissues. These observations provide evidence that HBO treatment has a powerful effect on the redox state of relevant tissues and produces an environment that inhibits oxidation. The anti-oxidant response may be the key to the anti-atherogenic effect of HBO treatment.
我们之前证明，高压氧（HBO）治疗可抑制新西兰白兔饮食诱导的动脉粥样硬化。在本研究中，我们在一种广泛认可的动脉粥样硬化模型——载脂蛋白E基因敲除（KO）小鼠中，研究了可能参与HBO治疗抗动脉粥样硬化作用的机制。我们检测了每日HBO治疗（持续5周和10周）对血液、肝脏和主动脉组织中抗氧化防御机制成分及氧化还原状态的影响，并将其与未治疗的载脂蛋白E基因敲除小鼠进行比较。HBO治疗导致主动脉胆固醇含量显著降低，脂肪条纹形成减少。这些变化伴随着针对氧化修饰低密度脂蛋白的自身抗体显著减少，以及肝脏和主动脉组织氧化还原状态的深刻改变。为期10周的治疗显著降低了肝脏中丙二醛和氧化型谷胱甘肽的水平，同时显著提高了还原型谷胱甘肽、谷胱甘肽还原酶（GR）、转移酶、硒依赖性谷胱甘肽过氧化物酶和过氧化氢酶（CAT）的水平。HBO治疗在主动脉组织中的作用相似。这些观察结果提供了证据，表明HBO治疗对相关组织的氧化还原状态有强大作用，并产生一个抑制氧化的环境。抗氧化反应可能是HBO治疗抗动脉粥样硬化作用的关键。
