Department of Pathophysiology, Xian Jiaotong University School of Medicine, Xian, Shannxi, PR China.
Reprod Sci. 2010 Jun;17(6):540-8. doi: 10.1177/1933719110364061. Epub 2010 Apr 1.
The prevalence of cerebral palsy (CP) shows little temporal or geographic variation and is associated with preterm birth, maternal/fetal infection/inflammation, and fetal growth restriction (IUGR), a potential surrogate for chronic fetal hypoxemia (CHX). We previously demonstrated CHX causes a fetal inflammatory response syndrome (FIRS). Herein, we test the hypothesis that CHX may cause fetal brain injury by upregulating inflammatory cytokine cascades, culminating in apoptosis pathway activation. Time-mated guinea pigs were housed in 12% or 10.5% O(2) for the last 21% of gestation. Chronic fetal hypoxemia increased the lactate/pyruvate and decreased the glutathione (GSH)/oxidized glutathione (GSSH) ratios, confirming a shift to a prooxidant state. The end result was a >30% decrease in hippocampal neuron density. Based on a microarray spotted with 113 cytokines and receptors, 22 genes were upregulated by CHX in proportion to the degree of hypoxia; the findings were confirmed by quantitative polymerase chain reaction (PCR). Thus, CHX triggers fetal brain inflammation inversely proportional to its severity characterized by increased apoptosis and neuronal loss. We suggest CHX fetal brain injury is not directly caused by oxygen deprivation but rather is an adaptive response that becomes maladaptive.
脑瘫（CP）的患病率几乎没有时间或地域变化，与早产、母体/胎儿感染/炎症和胎儿生长受限（IUGR）有关，后者可能是慢性胎儿缺氧（CHX）的替代指标。我们之前已经证明 CHX 会导致胎儿炎症反应综合征（FIRS）。在此，我们通过上调炎症细胞因子级联反应，最终激活细胞凋亡途径来检验 CHX 可能导致胎儿脑损伤的假说。在妊娠最后 21%的时间里，将时间匹配的豚鼠饲养在 12%或 10.5%的氧气中。慢性胎儿缺氧会增加乳酸/丙酮酸的比值，并降低谷胱甘肽（GSH）/氧化谷胱甘肽（GSSH）的比值，从而证实了向促氧化剂状态的转变。最终的结果是海马神经元密度下降了 30%以上。基于微阵列上的 113 种细胞因子和受体，CHX 上调了 22 个基因，其上调程度与缺氧程度成正比；定量聚合酶链反应（PCR）证实了这一发现。因此，CHX 引发的胎儿脑炎症与缺氧的严重程度成反比，其特征是细胞凋亡和神经元丢失增加。我们认为 CHX 对胎儿脑损伤不是直接由缺氧引起的，而是一种适应反应，但会变得适应不良。
