Perlmutter D H
Department of Pediatrics, Cell Biology and Physiology, Washington University, School of Medicine, St. Louis Children's Hospital, MO 63110, USA.
Ann Med. 1996 Oct;28(5):385-94. doi: 10.3109/07853899608999097.
Alpha-1-antitrypsin (alpha 1-AT) deficiency is a well known cause of emphysema in adults. A subgroup of deficient individuals develops liver injury during infancy and childhood. In fact, it is the most common genetic cause of liver disease in children. Although lung injury is due to the decrease in alpha 1-AT function in the lung, allowing uninhibited elastolytic destruction of its connective tissue integrity, liver injury is probably due to retention of the mutant alpha 1-AT molecule in the endoplasmic reticulum (ER) of liver cells. Recent studies have shown that the mutant alpha 1-AT molecule polymerizes in the ER by a novel loop-sheet insertion mechanism. Other recent studies show that the subgroup of deficient individuals is susceptible to liver injury by virtue of unlinked genetic traits and/or environmental factors which interfere with degradation of the mutant alpha 1-AT molecules within the ER.
α1 -抗胰蛋白酶（α1 - AT）缺乏是成人肺气肿的一个众所周知的病因。一部分缺乏α1 - AT的个体在婴儿期和儿童期会出现肝损伤。事实上，它是儿童肝病最常见的遗传病因。虽然肺损伤是由于肺中α1 - AT功能下降，导致其结缔组织完整性不受抑制地被弹性蛋白酶破坏，但肝损伤可能是由于突变的α1 - AT分子滞留在肝细胞的内质网（ER）中。最近的研究表明，突变的α1 - AT分子通过一种新的环片插入机制在内质网中聚合。其他近期研究表明，缺乏α1 - AT的个体亚组易患肝损伤，这是由于与降解内质网内突变的α1 - AT分子的过程相互干扰的非连锁遗传特征和/或环境因素所致。
