Role of apoptosis in the remodeling of cholestatic liver injury following release of the mechanical stress
Role of apoptosis in the remodeling of cholestatic liver injury following release of the mechanical stress
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DOI：
10.1007/s00428-003-0773-7
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发表时间：
2003-04-01
期刊：
影响因子：
3.5
通讯作者：
Desmoulière, A
中科院分区：
文献类型：
--
作者：
Costa, AMA;Tuchweber, B;Desmoulière, A
长期以来，人们已经知道实验性胆总管结扎后的门静脉纤维化在障碍物清除后是可逆的，但其机制仍不清楚。我们研究了胆十二指肠吻合术和单纯胆管减压术对胆管结扎大鼠病变重塑的影响。结扎大鼠胆总管7天或14天。胆管结扎14天后进行胆十二指肠吻合术，并间隔处死动物。在其他动物中，在结扎7天或14天后，仅通过胆汁抽吸减压胆总管，并在24小时后处死动物。评价胶原沉积、α-平滑肌肌动蛋白表达和细胞凋亡。收集胆汁并评估胆汁酸特征。吻合后，胶原沉积和α-平滑肌肌动蛋白表达下降，并在7天后恢复到对照值。这些参数在胆道减压后24小时几乎保持不变。胆管结扎本身诱导一些成纤维细胞和胆管细胞凋亡7天后，这是恢复正常后14天。吻合或减压后，成纤维细胞和胆管细胞凋亡均显著增加，并伴有细胞外基质降解的超微结构特征。胆总管结扎后总胆汁酸含量降低，二羟化胆汁酸比例降低，三羟化胆汁酸比例升高。胆道减压和吻合术并没有改变胆汁酸池的总浓度和组成。总之，我们发现单纯的胆道减压，通过减轻机械应力，是一样有效的胆十二指肠吻合术诱导门静脉细胞凋亡，可能触发门静脉纤维化消退。
It has been known for a long time that portal fibrosis consecutive to experimental common bile duct ligation is reversible following obstacle removal, but the mechanisms involved remain unknown. We have studied the effect of bilioduodenal anastomosis and of simple biliary decompression on the remodeling of the lesion in bile duct-ligated rats. Rats were subjected to common bile duct ligation for 7 days or 14 days. Bilioduodenal anastomosis was performed after 14 days of bile duct ligation and animals sacrificed at intervals. In other animals, after 7 days or 14 days of ligation, the common bile duct was merely decompressed by bile aspiration and animals sacrificed 24 h later. Collagen deposition, alpha-smooth muscle actin expression and apoptosis were evaluated. Bile was collected and the bile acid profile assessed. After anastomosis, collagen deposition and alpha-smooth muscle actin expression decreased and were back to control values after 7 days. These parameters remained practically unchanged 24 h after biliary decompression. Bile duct ligation by itself induced apoptosis of some fibroblastic and bile ductular cells after 7 days; this was back to normal after 14 days. After anastomosis or decompression, apoptosis of both fibroblastic and bile ductular cells increased greatly and was accompanied by ultrastructural features of extracellular matrix degradation. Total bile acid content decreased after common bile duct ligation, the proportion of dihydroxylated bile acids decreasing and that of trihydroxylated bile acids increasing. Biliary decompression and anastomosis did not modify total concentration and composition of the biliary bile acid pool. In summary, we show that mere biliary decompression, by relieving the mechanical stress, is as effective as bilioduodenal anastomosis to induce apoptosis of portal cells that likely triggers portal fibrosis regression.