Gibelli Nelson Elias Mendes, Tannuri Uenis, Mello Evandro Sobroza de
Pediatric Surgery and Pediatric Liver Transplantation Divisions, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2008 Oct;63(5):689-94. doi: 10.1590/s1807-59322008000500019.
Although there is much known about liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases observed in newborn infants and those in adults. For example, how do newborns respond to duct epithelial cell injury? Do the stellate cells in newborns respond similarly to those in adults during biliary obstruction?
Ninety newborn Wistar rats aged six days, weighing 8.0 - 13.9 g each, and 90 adult rats weighing 199.7 - 357.0 g each, were submitted to bile duct ligation. After surgery, they were randomly divided and sacrificed on the 3rd, 5th, 7th, 14th, 21st or 28th day post-bile duct ligation. Hepatic biopsies were obtained and immunohistochemical semi-quantification of desmin and alpha-SMA expression was performed in hepatic stellate cells and in myofibroblasts in the portal space, and between the portal space and the liver lobule.
Desmin expression in the myofibroblast cells post-bile duct ligation was higher in young rats, reaching its peak level in a shorter time when compared to the adult animals. The differences between the groups for alpha-SMA expression were less significant than for desmin.
These findings indicate that there is an increase in the number of collagen-producing myofibroblast cells in young animals, suggesting that there is more intense fibrosis in this population. This finding may explain why young animals with bile duct obstruction experience more intense portal fibrosis that is similar to the pathology observed in the livers of newborns with biliary atresia.
尽管对肝脏疾病已有诸多了解,但仍有一些方面尚不清楚,例如新生儿所患肝病与成人所患肝病之间差异的本质。例如,新生儿如何应对胆管上皮细胞损伤?在胆管梗阻期间,新生儿的星状细胞反应与成人的星状细胞反应是否相似?
选取90只6日龄的新生Wistar大鼠,每只体重8.0 - 13.9克,以及90只成年大鼠,每只体重199.7 - 357.0克,进行胆管结扎。术后,将它们随机分组,并在胆管结扎后的第3、5、7、14、21或28天处死。获取肝脏活检组织,对肝星状细胞以及门管区和门管区与肝小叶之间的肌成纤维细胞中的结蛋白和α - 平滑肌肌动蛋白(α - SMA)表达进行免疫组织化学半定量分析。
胆管结扎后,肌成纤维细胞中的结蛋白表达在幼鼠中较高,与成年动物相比,其在更短时间内达到峰值水平。α - SMA表达的组间差异不如结蛋白的差异显著。
这些发现表明幼龄动物中产生胶原蛋白的肌成纤维细胞数量增加,提示该群体中纤维化更严重。这一发现可能解释了为什么胆管梗阻的幼龄动物会经历更严重的门脉纤维化,这与胆道闭锁新生儿肝脏中观察到的病理情况相似。