Aronson D C, Chamuleau R A, Frederiks W M, Gooszen H G, Heijmans H S, James J
Department of Surgery, Academic Hospital, University of Leiden, The Netherlands.
J Hepatol. 1993 Apr;18(1):85-95. doi: 10.1016/s0168-8278(05)80014-5.
In 36 male Wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledochojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor X were measured weekly. Liver biopsies were taken at the time of restored bile flow as well as 3 and 8 weeks thereafter. Histochemical reaction for lactate dehydrogenase activity and Sirius Red F3BA staining were used as measure for functional liver parenchyma and collagen, respectively. Acid phosphatase, alkaline phosphatase and 5'-nucleotidase activities as well as the glycogen content were demonstrated in cryostat sections of the same biopsies. After 1, 2 and 3 weeks of common bile duct obstruction, levels of bilirubin, alkaline phosphatase and GOT significantly increased, whereas levels of clotting factor X decreased. RBF resulted in normalization of all these levels to control range. The volume density of functional parenchyma was found to be reduced to 90%, 73% and 64% of the control values following 1, 2 and 3 weeks of common bile duct obstruction respectively, returning to 96%, 94% and 88% at 8 weeks, respectively, after restored bile flow. The collagen content increased significantly during cholestasis up to 5-fold after 3 weeks of common bile duct obstruction. After restored bile flow, a slight decrease of collagen was measured in some animals but in none of the three groups a return to normal values appeared. Cholestasis induced an alteration in localization and/or activity of the three enzymes analyzed as well as a depletion of glycogen stores. All changes in activity and distribution pattern of the three enzymes, as well as the glycogen depletion during common bile duct obstruction normalised after restored bile flow was performed. However, the longer common bile duct obstruction had existed, the longer period was needed for full recovery. In conclusion, even after 3 weeks of common bile duct obstruction the parenchyma/stroma relationship grossly normalized after restored bile flow with an almost complete restoration of the parenchyma and a concomitant recovery of liver function. However, collagen once formed, did not disappear but remained as more condensed septa, which apparently did not interfere with normal function.
在36只雄性Wistar大鼠中，通过结扎和横断胆总管诱导肝外胆汁淤积。胆汁淤积1、2和3周后，通过Roux-en-Y胆总管空肠吻合术恢复胆汁流动。每周测量血浆胆红素、碱性磷酸酶、谷草转氨酶和凝血因子X的水平。在恢复胆汁流动时以及此后3周和8周时进行肝脏活检。分别使用乳酸脱氢酶活性的组织化学反应和天狼星红F3BA染色作为功能性肝实质和胶原蛋白的测量方法。在相同活检的低温切片中显示酸性磷酸酶、碱性磷酸酶和5'-核苷酸酶活性以及糖原含量。胆总管梗阻1、2和3周后，胆红素、碱性磷酸酶和谷草转氨酶水平显著升高，而凝血因子X水平降低。RBF使所有这些水平恢复到对照范围。发现功能性实质的体积密度在胆总管梗阻1、2和3周后分别降至对照值的90%、73%和64%，胆汁流动恢复后8周时分别恢复至96%、94%和88%。胆汁淤积期间胶原蛋白含量显著增加，胆总管梗阻3周后增加至5倍。胆汁流动恢复后，在一些动物中测量到胶原蛋白略有下降，但三组中均未出现恢复至正常值的情况。胆汁淤积导致所分析的三种酶的定位和/或活性发生改变以及糖原储备耗竭。在进行胆汁流动恢复后，胆总管梗阻期间三种酶的活性和分布模式的所有变化以及糖原耗竭均恢复正常。然而，胆总管梗阻存在的时间越长，完全恢复所需的时间就越长。总之，即使在胆总管梗阻3周后，胆汁流动恢复后实质/基质关系大体上恢复正常，实质几乎完全恢复且肝功能随之恢复。然而，一旦形成的胶原蛋白不会消失，而是作为更致密的间隔保留下来，显然这不会干扰正常功能。
