Sant'Anna L B, Brito F S, Barja P R, Nicodemo M C
Laboratório de Histologia e Terapia Regenerativa, Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, São José dos Campos, SP, Brasil.
Laboratório de Fotoacústica Aplicada aos Sistemas Biológicos, Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, São José dos Campos, SP, Brasil.
Braz J Med Biol Res. 2017 Jul 3;50(7):e5692. doi: 10.1590/1414-431X20175692.
Liver fibrosis is the most common outcome of chronic liver diseases, and its progression to cirrhosis can only be effectively treated with liver transplantation. The amniotic membrane (AM) has been studied as an alternative therapy for fibrosis diseases mainly for its favorable properties, including anti-inflammatory, anti-scaring and immunomodulatory properties. It was recently demonstrated that the AM reduces the progression of biliary fibrosis to its advanced stage, cirrhosis, when applied on the liver for 6 weeks after fibrosis induction. Here, we investigated the effects of AM on rat fibrotic liver, during a prolonged period of time. Fibrosis was induced by bile duct ligation (BDL), and at the same time, a fragment of AM was applied around the liver. After 1, 3, 6, and 9 weeks, the degree of fibrosis was assessed by qualitative Knodell scoring, and by quantitative image analysis to quantify the area of collagen deposition in hepatic tissue. While fibrosis progressed rapidly in untreated BDL animals, leading to cirrhosis within 6 weeks, AM-treated livers showed confined fibrosis at the periportal area with few and thin fibrotic septa, but without cirrhosis. In addition, collagen deposition was reduced to about 36 and 55% of levels observed in BDL at 6 and 9 weeks after BDL, respectively, which shows that the longer the period of AM application, the lower the collagen deposition. These results suggested that AM applied as a patch onto the liver surface for longer periods attenuated the severity of biliary fibrosis and protected against liver degeneration caused by excessive collagen deposition.
肝纤维化是慢性肝病最常见的结局，其进展为肝硬化时，只有通过肝移植才能得到有效治疗。羊膜（AM）因其具有抗炎、抗瘢痕和免疫调节等良好特性，已被作为纤维化疾病的一种替代疗法进行研究。最近有研究表明，在诱导纤维化后，将羊膜应用于肝脏6周，可减少胆管纤维化进展至晚期肝硬化。在此，我们研究了羊膜在较长时间内对大鼠纤维化肝脏的影响。通过胆管结扎（BDL）诱导纤维化，同时将一片羊膜应用于肝脏周围。在1、3、6和9周后，通过定性的Knodell评分以及定量图像分析来评估纤维化程度，以量化肝组织中胶原沉积的面积。未治疗的BDL动物纤维化进展迅速，在6周内发展为肝硬化，而接受羊膜治疗的肝脏在门静脉周围区域显示局限性纤维化，纤维化间隔少且薄，但未出现肝硬化。此外，胶原沉积在BDL后6周和9周分别降至BDL组观察水平的约36%和55%，这表明羊膜应用时间越长，胶原沉积越低。这些结果表明，将羊膜作为贴片长时间应用于肝脏表面可减轻胆管纤维化的严重程度，并防止因过度胶原沉积导致的肝脏退变。
