Neonatal Research Unit Q2:07, Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
Pediatr Res. 2012 Nov;72(5):460-7. doi: 10.1038/pr.2012.119. Epub 2012 Aug 27.
Apnea associated with infection and inflammation is a major medical concern in preterm infants. Prostaglandin E(2) (PGE(2)) serves as a critical mediator between infection and apnea. We hypothesize that alteration of the microsomal PGE synthase-1 (mPGES-1) PGE(2) pathway influences respiratory control and response to hypoxia.
Nine-d-old wild-type (WT) mice, mPGES-1 heterozygote (mPGES-1(+/-)), and mPGES-1 knockout (mPGES-1(-/-)) mice were used. Respiration was investigated in mice using flow plethysmography after the mice received either interleukin-1β (IL-1β) (10 µg/kg) or saline. Mice were subjected to a period of normoxia, subsequent exposure to hyperoxia, and finally either moderate (5 min) or severe hypoxia (until 1 min after last gasp).
IL-1β worsened survival in WT mice but not in mice with reduced or no mPGES-1. Reduced expression of mPGES-1 prolonged gasping duration and increased the number of gasps during hypoxia. Response to intracerebroventricular PGE(2) was not dependent on mPGES-1 expression.
Activation of mPGES-1 is involved in the rapid and vital response to severe hypoxia as well as inflammation. Attenuation of mPGES-1 appears to have no detrimental effects, yet prolongs autoresuscitation efforts and improves survival. Consequently, inhibition of the mPGES-1 pathway may serve as a potential therapeutic target for the treatment of apnea and respiratory disorders.
与感染和炎症相关的呼吸暂停是早产儿的一个主要医学关注点。前列腺素 E2（PGE2）作为感染和呼吸暂停之间的关键介质。我们假设微粒体前列腺素 E 合酶-1（mPGES-1）PGE2 途径的改变会影响呼吸控制和对缺氧的反应。
使用 9 天大的野生型（WT）小鼠、mPGES-1 杂合子（mPGES-1(+/-)）和 mPGES-1 敲除（mPGES-1(-/-)）小鼠进行研究。在给小鼠注射白细胞介素-1β（IL-1β）（10μg/kg）或生理盐水后，使用流量描记法研究小鼠的呼吸情况。小鼠首先经历一段正常氧期，随后暴露于高氧环境，最后是中度（5 分钟）或重度缺氧（直到最后一次喘息后 1 分钟）。
IL-1β使 WT 小鼠的存活率降低，但对 mPGES-1 表达减少或缺失的小鼠没有影响。mPGES-1 表达减少延长了喘息持续时间，并增加了缺氧期间的喘息次数。对脑室内 PGE2 的反应不依赖于 mPGES-1 的表达。
mPGES-1 的激活参与了对严重缺氧以及炎症的快速和重要反应。mPGES-1 的衰减似乎没有不利影响，但延长了自主复苏的努力并提高了存活率。因此，抑制 mPGES-1 途径可能成为治疗呼吸暂停和呼吸障碍的潜在治疗靶点。
