Institut Pasteur de Dakar, Dakar, Senegal.
Malar J. 2010 Feb 9;9:45. doi: 10.1186/1475-2875-9-45.
Placental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta.
Placental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR.
COX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively), whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2.
These data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection.
胎盘疟疾(PM)与胎儿发育不良有关,但涉及的病理生理过程知之甚少。环氧化酶(COX)和脂氧合酶(LOX)将脂肪酸转化为前列腺素和白三烯,在妊娠和胎儿发育中发挥重要作用。COX-2 目前是特定药物的靶向目标,它具有双重作用,因为它与子痫前期病理和感染期间的恢复有关。通过定量分析两组疟疾感染和未感染胎盘在分娩时的 COX-1、COX-2、15-LOX 和 IL-10 表达,质疑了 COX 在 PM 中的作用。
分娩时采集胎盘活检进行 mRNA 分离和定量,使用实时 PCR。
COX-2 和 IL-10 mRNA 主要在慢性感染期间增加(分别增加了九倍和五倍),而 COX-1 转录物保持不变。COX-2 的过度表达与婴儿出生体重增加有关,但与母亲血红蛋白水平降低有关。它与胎盘巨噬细胞浸润和低血色素沉着有关。相反,胎盘感染与 15-LOX mRNA 的表达降低有关。高程度的血色素沉着与低出生体重和 COX-2 表达降低有关。
这些数据提供了证据表明 COX-2 和 IL-10 在胎盘慢性感染期间高度诱导,但与早产或低出生体重无关。这些数据支持 COX-2 参与胎盘感染的恢复阶段。