Scherer Emilene B S, da Cunha Aline Andrea, Kolling Janaína, da Cunha Maira J, Schmitz Felipe, Sitta Angela, Lima Daniela D, Delwing Débora, Vargas Carmem R, Wyse Angela T S
Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2011 Nov;29(7):693-9. doi: 10.1016/j.ijdevneu.2011.06.004. Epub 2011 Jun 16.
The purpose of this study was to develop a chronic chemically induced model of mild hyperhomocysteinemia in adult rats. We produced levels of Hcy in the blood (30μM), comparable to those considered a risk factor for the development of neurological and cardiovascular diseases, by injecting homocysteine subcutaneously (0.03μmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Using this model, we evaluated the effect of chronic administration of homocysteine on redox status in the blood and cerebral cortex of adult rats. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in the plasma and cerebral cortex, while nitrite levels were reduced in the cerebral cortex, but not in the plasma, of rats subjected to chronic mild hyperhomocysteinemia. Homocysteine was also seen to disrupt enzymatic and non-enzymatic antioxidant defenses in the blood and cerebral cortex of rats. Since experimental animal models are useful for understanding the pathophysiology of human diseases, the present model of mild hyperhomocysteinemia may be useful for the investigation of additional mechanisms involved in tissue alterations caused by homocysteine.
本研究的目的是建立成年大鼠慢性化学诱导的轻度高同型半胱氨酸血症模型。从产后第30天至第60天，每天两次皮下注射同型半胱氨酸（0.03μmol/g体重），使血液中的同型半胱氨酸水平达到30μM，这一水平与被认为是神经和心血管疾病发生风险因素的水平相当。对照组注射相同体积的生理盐水。利用该模型，我们评估了慢性给予同型半胱氨酸对成年大鼠血液和大脑皮层氧化还原状态的影响。在慢性轻度高同型半胱氨酸血症大鼠的血浆和大脑皮层中，活性氧和硫代巴比妥酸反应性物质显著增加，而大脑皮层中的亚硝酸盐水平降低，但血浆中未降低。同型半胱氨酸还被发现会破坏大鼠血液和大脑皮层中的酶促和非酶促抗氧化防御。由于实验动物模型有助于理解人类疾病的病理生理学，目前的轻度高同型半胱氨酸血症模型可能有助于研究同型半胱氨酸引起组织改变的其他机制。
