Barth A, Bauer R, Kluge H, Gedrange T, Walter B, Klinger W, Zwiener U
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany.
Exp Toxicol Pathol. 1995 May;47(2-3):139-47. doi: 10.1016/S0940-2993(11)80302-7.
In order to investigate the pathogenetic factors causing the relatively frequent occurrence of brain injury in intrauterine growth-restricted newborns, lipid peroxidation products (TBAR), glutathione (GSH, GSSG) and in vitro production of reactive oxygen species (chemiluminescence, stimulated lipid peroxidation, H2O2 formation) were studied in the brain of normal weight (NW) and intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour of hypoxia (FiO2 11%) and 90 min reoxygenation. Cardiocirculatory parameters and catecholamine release into the blood were also measured. In the cerebellum, higher GSH content, but also higher in vitro production of lucigenin amplified chemiluminescence were found in comparison to other brain regions, independent of growth restriction and hypoxia. Moderate hypoxia without acidosis and hypercapnia resulted in GSH depletion especially in the brain of IUGR, but no changes in GSSG concentrations were measured. Though TBAR decreased after hypoxia/reoxygenation, in some brain areas of IUGR higher TBAR values were found in comparison to NW. H2O2 formation, stimulated lipid peroxidation and lucigenin and luminol amplified chemiluminescence in the 9000 x/g supernatant of brain tissue did not reveal special response of IUGR to hypoxia/reoxygenation. Hypoxia-induced circulatory centralisation due to increased release of catecholamines into the plasma prevented oxygen deficiency also in the brain of IUGR. The role of brain monoamine metabolism in the production of reactive oxygen species, followed by greater GSH depletion and higher in vivo formation of lipid peroxides in IUGR is discussed.
为了研究导致宫内生长受限新生儿脑损伤相对频繁发生的致病因素，我们对正常体重（NW）和宫内生长受限新生仔猪（IUGR）在缺氧1小时（FiO2 11%）和复氧90分钟后，检测了其脑内的脂质过氧化产物（TBAR）、谷胱甘肽（GSH、GSSG）以及活性氧的体外生成（化学发光、刺激脂质过氧化、H2O2形成）。还测量了心脏循环参数和血液中儿茶酚胺的释放。在小脑中，与其他脑区相比，无论生长受限和缺氧情况如何，均发现其GSH含量较高，但荧光素酶增强化学发光的体外生成也较高。无酸中毒和高碳酸血症的中度缺氧导致GSH耗竭，尤其是在IUGR的脑中，但未检测到GSSG浓度的变化。尽管缺氧/复氧后TBAR降低，但与NW相比，在IUGR的一些脑区中发现TBAR值较高。脑组织9000×g上清液中的H2O2形成、刺激脂质过氧化以及荧光素酶和鲁米诺增强化学发光均未显示IUGR对缺氧/复氧有特殊反应。缺氧诱导的循环集中化是由于血浆中儿茶酚胺释放增加，这也防止了IUGR脑中的缺氧。本文讨论了脑单胺代谢在活性氧生成中的作用，随后IUGR中出现更大的GSH耗竭和更高的脂质过氧化物体内形成。
