血小板活化因子在新生儿坏死性小肠结肠炎发病中的作用

坏死性小肠结肠炎是新生儿,尤其是早产儿或极低出生体重儿最常见的胃肠道急症,至今仍是早产儿发病和死亡最常见的原因.大量流行病学、动物实验模型及临床研究发现NEC是与早产、配方奶喂养、肠缺血缺氧、细菌异常增殖等多种因素相互作用的结果,但其确切的发病机制尚不完全清楚.目前有研究者通过模拟上述因素建立NEC动物模型,发现模型鼠中NEC组回肠中血小板活化因子水平较对照组明显升高,予以PAF拮抗剂预处理后NEC的发病率显著降低,表明PAF在NEC发病中有关键作用.PAF通过与其受体特异性结合后,可激活多条信号传导通路,导致多种炎症介质合成与释放增加;肠道黏膜屏障受损,大量毒素吸收,进一步增加内源性PAF合成;通过依赖线粒体途径凋亡肠上皮细胞;激活核因子NF-κB通路放大级联炎症反应;诱导活性氧产生,引起细胞凋亡导致肠管坏死.

Roles of platelet-activating factor in the pathogenesis of neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most common cause of gastrointestinal emergencies in neonates,especially premature infants or very low birth weight infants,and is still the most common cause of morbidity and mortality in premature infants.The results including found by epidemiological,animal experimental models and clinical studies show that NEC is the results of premature,formula feeding,intestinal ischemia/hypoxia,and bacterial dislocation.However its exact pathogenesis is not entirely clear.Animal model of NEC imitated by above factors indicate that the levels of platelet-activating factor (PAF) in intestinal was increased,and the incidence of NEC was decreased by treatment with PAF antagonist.PAF activate lots of signal transduction pathways through binding with its receptor,and then increase production and release of inflammatory mediators in intestinal,and absorb toxins through the injured mucosal barrier,then increase the synthesis of endogenous PAF,and damage intestinal epithelial cells by mitochondrial pathway and reactive oxygen species,and amplify the cascade inflammatory reaction through activation of nuclear factor NF-κB.