Frøen J Frederik, Munkeby Berit H, Stray-Pedersen Babill, Saugstad Ola Didrik
Department of Pediatric Research, The National Hospital, University of Oslo, N-0027 Oslo, Norway.
Brain Res. 2002 Jun 28;942(1-2):87-94. doi: 10.1016/s0006-8993(02)02700-2.
Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Antibiotics have proven futile in reducing perinatal brain injuries. We tested whether treatment with the anti-inflammatory cytokine IL-10 could have beneficial effects during a concomitant endotoxin and cerebral hypoxic-ischemic challenge. Thirty-three newborn piglets were randomized to pretreatment with:
placebo, Endotoxin: 2 kU/kg bolus and infusion of 1 kU/kg per h of endotoxin, or Endotoxin+IL-10: endotoxin in addition to 50 microg/kg of porcine recombinant IL-10. We induced cerebral hypoxia-ischemia by bilateral clamping of the common carotid arteries and ventilation with 8% oxygen for 20 min followed by 3 h of reoxygenation/reperfusion. Extracellular lactate, pyruvate, glycerol and glutamate, microcirculation and tissue oxygenation were monitored in the striatum by microdialysis, laser Doppler flow and oxygen tension probe, respectively. During and/or after cerebral hypoxia-ischemia, Endotoxin caused marked deterioration of the cerebral metabolic situation with higher lactate/pyruvate ratio (P=0.003), compared to CONTROLS and Endotoxin+IL-10. This was caused mainly by very low levels of pyruvate (P=0.001). During the following reoxygenation, Endotoxin compromised cerebral microcirculation (P=0.038) and tissue oxygenation (P=0.012) compared to CONTROLS and Endotoxin+IL-10. After a period of remission, a secondary energy failure and a new rise in the lactate/pyruvate ratio was seen in Endotoxin (P=0.002), but not in CONTROLS or Endotoxin+IL-10. At the end of observation, only the Endotoxin+IL-10 group had regained their baseline values in all variables. Thus IL-10 counteracts acute effects of endotoxin on cerebral metabolism, microcirculation and oxygen tension during hypoxia-ischemia in the perinatal brain.
围产期脑损伤及随后脑瘫的发生与宫内感染和炎症反应密切相关。抗生素已被证明在减少围产期脑损伤方面无效。我们测试了在同时存在内毒素和脑缺氧缺血挑战期间，用抗炎细胞因子白细胞介素 -10进行治疗是否会产生有益效果。33只新生仔猪被随机分为以下预处理组：
安慰剂；内毒素组：2 kU/kg推注及每小时输注1 kU/kg内毒素；内毒素 + 白细胞介素 -10组：除50 μg/kg猪重组白细胞介素 -10外，给予内毒素。通过双侧夹闭颈总动脉并以8%氧气通气20分钟，随后进行3小时的再氧合/再灌注来诱导脑缺氧缺血。分别通过微透析、激光多普勒血流仪和氧张力探头监测纹状体内的细胞外乳酸、丙酮酸、甘油和谷氨酸、微循环和组织氧合情况。在脑缺氧缺血期间和/或之后，与对照组和内毒素 + 白细胞介素 -10组相比，内毒素导致脑代谢状况明显恶化，乳酸/丙酮酸比值更高（P = 0.003）。这主要是由于丙酮酸水平极低（P = 0.001）。在随后的再氧合过程中，与对照组和内毒素 + 白细胞介素 -10组相比，内毒素损害了脑微循环（P = 0.038）和组织氧合（P = 0.012）。经过一段时间的缓解后，在内毒素组中出现了继发性能量衰竭和乳酸/丙酮酸比值的再次升高（P = 0.002），而在对照组或内毒素 + 白细胞介素 -10组中未出现。在观察结束时，只有内毒素 + 白细胞介素 -10组的所有变量都恢复到了基线值。因此，白细胞介素 -10可抵消围产期脑缺氧缺血期间内毒素对脑代谢、微循环和氧张力的急性影响。
