da Cunha Maira J, da Cunha Aline A, Loureiro Samanta O, Machado Fernanda R, Schmitz Felipe, Kolling Janaína, Marques Eduardo P, Wyse Angela T S
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Mol Neurobiol. 2015 Dec;52(3):1590-1600. doi: 10.1007/s12035-014-8961-9. Epub 2014 Nov 4.
In the present study, we investigate the effect of lung injury on parameters of oxidative/nitrative stress [reactive oxygen species production, nitrite levels, thiobarbituric acid-reactive substances (TBARS), carbonyl content, sulfhydryl content, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), total radical-trapping antioxidant potential, glutathione content, and glucose-6-phosphate dehydrogenase], as well as on inflammation mediators [immunocontent of nuclear factor-kappaB (NF-κB) total (p65), NF-κB phosphorylated (pp65) subunit (cytosolic and nuclear), TNF-α, IL-1β, IL-6, and IL-10] in the cerebral cortex. Cytokine levels in serum were also evaluated. Adult Wistar rats were submitted to lung injury induced by intratracheal instillation of lipopolysaccharide in a dose of 100 μg/100 g body weight. Sham group (control) received isotonic saline instillation. Twelve hours after the injury, rats were decapitated and blood samples were collected and the cerebral cortex dissected out. Results showed an increase in reactive oxygen species production, TBARS, and nitrite and carbonyl levels in the cerebral cortex of rats submitted to lung injury. Antioxidant enzymatic defenses were altered, superoxide dismutase and glutathione peroxidase activities decreased, and catalase activity increased. Non-enzymatic antioxidant capacity, glutathione content, and glucose-6-phosphate dehydrogenase were decreased. Inflammatory parameters were also altered in the cerebral cortex of rats subjected to lung injury; it was observed an increase in the immunocontent of NF-κB/p65 (nuclear fraction) and NF-κB/pp65 (cytosolic and nuclear faction), as well as an increase in TNF-α, IL-1β, IL-6, and IL-10 levels. The levels of IL-10 also increased in the serum. Our findings show that the lung injury alters oxidative/nitrative status and induces inflammation in the cerebral cortex of rats, which might be associated with cognitive impairments present in patients with lung injury.
在本研究中，我们调查了肺损伤对氧化/硝化应激参数[活性氧生成、亚硝酸盐水平、硫代巴比妥酸反应性物质（TBARS）、羰基含量、巯基含量、抗氧化酶（超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）活性、总自由基捕获抗氧化能力、谷胱甘肽含量和葡萄糖-6-磷酸脱氢酶]的影响，以及对大脑皮质中炎症介质[核因子-κB（NF-κB）总量（p65）、NF-κB磷酸化（pp65）亚基（胞质和核）、TNF-α、IL-1β、IL-6和IL-10的免疫含量]的影响。还评估了血清中的细胞因子水平。成年Wistar大鼠通过气管内滴注剂量为100μg/100g体重的脂多糖诱导肺损伤。假手术组（对照组）接受等渗盐水滴注。损伤12小时后，将大鼠断头，采集血样并取出大脑皮质。结果显示，遭受肺损伤的大鼠大脑皮质中活性氧生成、TBARS以及亚硝酸盐和羰基水平增加。抗氧化酶防御功能发生改变，超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低，而过氧化氢酶活性增加。非酶抗氧化能力、谷胱甘肽含量和葡萄糖-6-磷酸脱氢酶降低。遭受肺损伤的大鼠大脑皮质中的炎症参数也发生改变；观察到NF-κB/p65（核部分）和NF-κB/pp65（胞质和核部分）的免疫含量增加，以及TNF-α、IL-1β、IL-6和IL-10水平增加。血清中IL-10水平也升高。我们的研究结果表明，肺损伤会改变大鼠大脑皮质的氧化/硝化状态并诱导炎症，这可能与肺损伤患者出现的认知障碍有关。
