Fritz Karen I, Zubrow Alan B, Ashraf Qazi M, Mishra Om P, Delivoria-Papadopoulos Maria
Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Neonatology Research Laboratories, Philadelphia, Pennsylvania 19134, USA.
Neurochem Res. 2004 Apr;29(4):791-6. doi: 10.1023/b:nere.0000018852.85899.85.
Previous studies have shown that hypocapnia results in fragmentation of nuclear DNA in the cerebral cortex of newborn piglets. We tested the hypothesis that hypocapnia results in decreased ATP and phosphocreatine (PCr) levels and increased nuclear high-affinity Ca++-ATPase activity, intranuclear Ca++ flux, and CaM kinase IV activity in neuronal nuclei of piglets. Three groups of piglets were ventilated as either hypocapnic (a PaCO2 of 20 mm Hg), normocapnic (a PaCO2 of 40 mm Hg), or corrected hypocapnic (ventilated as hypocapnic but with CO2 added to maintain normocapnia) for 1 h. Tissue ATP levels were lower in the hypocapnic than in the normocapnic group. PCr levels were lower and 45Ca++-influx, Ca++-ATPase activity and CaM kinase IV activity were higher in hypocapnic than in normocapnic or corrected hypocapnic piglets. We conclude that hypocapnia alters nuclear membrane Ca++ flux mechanisms and may alter neuronal phosphorylation mechanisms in the cerebral cortex of piglets.
先前的研究表明,低碳酸血症会导致新生仔猪大脑皮质细胞核DNA碎片化。我们检验了以下假设:低碳酸血症会导致仔猪神经元细胞核中ATP和磷酸肌酸(PCr)水平降低,以及细胞核高亲和力Ca++-ATP酶活性、核内Ca++通量和CaM激酶IV活性增加。三组仔猪分别进行1小时的低碳酸血症通气(动脉血二氧化碳分压[PaCO2]为20 mmHg)、正常碳酸血症通气(PaCO2为40 mmHg)或纠正性低碳酸血症通气(以低碳酸血症方式通气,但添加二氧化碳以维持正常碳酸血症)。低碳酸血症组的组织ATP水平低于正常碳酸血症组。与正常碳酸血症或纠正性低碳酸血症仔猪相比,低碳酸血症仔猪的PCr水平更低,45Ca++通量、Ca++-ATP酶活性和CaM激酶IV活性更高。我们得出结论,低碳酸血症会改变核膜Ca++通量机制,并可能改变仔猪大脑皮质中的神经元磷酸化机制。