上皮间充质转化机制在胆道闭锁纤维化中的研究要点.doc

上皮间充质转化机制在胆道闭锁纤维化中的研究 ABSTRACT就BA的病因学的最新研究进展作一综述。 INTRODUCTION 胆道闭锁（biliary atresia, BA）是新生儿时期原因不明的一类胆汁淤积性疾病，出生一个月后逐渐出现体重增长缓慢、皮肤黄染、无胆色粪和肝脏肿大等典型的胆道梗阻表现。患者肝脏病理特点为不同程度的炎症浸润伴有毛细胆管增生，胆汁淤积及间充质组织增多。如果在2-3个月时早期诊断，可以通过Kasai术重建胆汁引流系统，成功率可达80% (1–3). 尽管目前手术成功率较高，在胆道重建术(Kasai术)后患儿的肝脏病变也将持续进展，主要表现为不同程度的毛细胆管炎症、纤维化并进行性加重，最终导致肝硬化。数据统计, 术后2年70–80% 患者需要肝脏移植, 因此，目前BA是儿童期肝移植的最常见原因，50%以上的儿童肝移植原发病变为胆道闭锁[5, 6]. 就胆道闭锁疾病的发病机制而言，现在更倾向于解释为，是由多种因素的综合作用而导致的胆管系统的进行性病变 (1,7)。需要强调的是胆道闭锁并不是单纯的肝外胆管纤维化梗阻性疾病，与之伴随的肝内胆道系统进行性的病变决定着患者的预后和最终结果。所以Kasai术的成功后，接踵而来的便是如何提高自体肝存活率的问题；因此需要对胆道闭锁中自体肝纤维化的病因及发病机制进行深入的探讨。对大量历史文献阅读后，提出肝内中小型胆管上皮细胞发生了上皮间充质转化，并最终导致肝内胆管增生和纤维化的假设。Without a better understanding of the etiology and pathogenesis发病机制 of this intrahepatic 胆管硬化sclerosing cholangitic process in BA, little progress can be expected in improving the nontransplantation outcome of patients. Therefore, there has been a renewed interest in recent years in understanding the underlying pathogenetic mechanisms of BA.It is now apparent that BA is a phenotype resulting from several pathogenic processes that culminate in obstruction of the biliary tree (1,7). The majority (80%) of cases of BA in Western countries are of the perinatal or acquired form. These most commonly involving abdominal situs, and has been dubbed the embryonic or fetal form. Defective morphogenesis, caused by mutations in genes regulating biliary development, has been proposed in these cases. In otherwise normal infants are presumably born with a patent biliary system which undergoes progressive inflammation and fibro-obliteration initiated by a perinatal insult. Although the etiology of this form is not completely understood, proposed precipitating factors include infectious, toxic, vascular, and immune mediators. The second form of BA is associated with other congenital anomalies, most this review, we will examine recent data supporting the proposed viral and immunologic pathogenesis of the perinatal form of BA, and the potential role for defective geneti