Vidyasagar D, Zagariya A
Division of Neonatology, Department of Pediatrics, The University of Illinois at Chicago, Chicago, IL 60517, USA.
J Perinatol. 2008 Dec;28 Suppl 3:S102-7. doi: 10.1038/jp.2008.153.
To review current literature related to cellular mechanisms of meconium-induced lung injury (MILI). Review of published experimental in vitro and in vivo MAS studies using human and animal lung cells. We found that meconium induces expression of cytokines and angiotensin II (ANG II)-induced apoptotic process in the lung cells. We postulate that inflammatory cytokines induce ANG II expression, which causes apoptotic cell death after binding to its AT1 receptors. We also demonstrated expression of serpins associated with meconium instillation into the lungs. Serpins are proteins that inhibit cellular proteases and elastases. Expression of serpins may be an attempt to recover lung from these injurious effects. In summary our studies show that whereas meconium induces inflammatory cytokines and subsequent cell apoptosis, the lung cells also try to protect themselves by inducing serpins. The balance of these interactions will determine the residual damage. We believe these new findings are very important in understanding of MILI.
回顾与胎粪吸入所致肺损伤(MILI)细胞机制相关的当前文献。对已发表的使用人和动物肺细胞进行的体外和体内MAS实验研究进行综述。我们发现胎粪可诱导肺细胞中细胞因子的表达以及血管紧张素II(ANG II)诱导的凋亡过程。我们推测炎性细胞因子诱导ANG II表达,ANG II与其AT1受体结合后导致细胞凋亡。我们还证实了与向肺内滴注胎粪相关的丝氨酸蛋白酶抑制剂(serpins)的表达。丝氨酸蛋白酶抑制剂是抑制细胞蛋白酶和弹性蛋白酶的蛋白质。丝氨酸蛋白酶抑制剂的表达可能是肺从这些损伤效应中恢复的一种尝试。总之,我们的研究表明,虽然胎粪可诱导炎性细胞因子及随后的细胞凋亡,但肺细胞也试图通过诱导丝氨酸蛋白酶抑制剂来保护自身。这些相互作用的平衡将决定残余损伤程度。我们认为这些新发现对于理解MILI非常重要。