Structural and functional alterations of hepatocytes during transient phalloidin-induced cholestasis in the rat.
Structural and functional alterations of hepatocytes during transient phalloidin-induced cholestasis in the rat.
复制标题
大鼠短暂性鬼笔环肽诱导的胆汁淤积期间肝细胞的结构和功能变化。
DOI：
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发表时间：
1996
影响因子：
3.8
通讯作者：
B. Tuchweber
中科院分区：
文献类型：
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作者：
A. Loranger;Claude Barriault;I. Yousef;B. Tuchweber
为了研究动态肌动蛋白网与胆汁分泌之间的关系，我们使用鬼笔环肽开发了急性胆汁淤积模型，并检查了大鼠肝脏中的连续形态和生化事件。在注射后 15、45 和 90 分钟、24 小时和 5 天评估大鼠单次静脉注射鬼笔环肽（0.8 mg/kg 体重）的胆功能（咬流、胆汁和胆管膜成分）和细胞完整性（血清和胆汁中肝酶的释放、胆管结构和微丝分布）。胆汁流量在 45 和 90 分钟时显着减少，但胆汁淤积是短暂的，因为胆汁分泌在 24 小时时恢复到控制水平。胆汁胆汁酸分泌率在同一时间段内没有改变，表明胆汁淤积可能是由于胆汁流中不依赖于胆汁酸的成分受损所致。血清丙氨酸氨基转移酶和乳酸脱氢酶以及胆汁碱性磷酸酶和碱性磷酸二酯酶 1 活性未因鬼笔环肽处理而改变。这些数据与形态学研究相结合，没有提供细胞损伤的证据。电镜显示，注射鬼笔环肽后，小叶中心和汇管周围肝细胞中的细管周围肌动蛋白网在 90 分钟时增加，并在 24 小时和 5 天时进一步扩大。在所有时期，小管结构都保存完好。富含胆小管复合物的膜组分中的 Na+K+ -ATPase 和 Mg2+ -ATPase 活性在 15 分钟时显着下降，直到第 5 天仍保持较低水平。到第 5 天，Mg2+ -ATPase 活性恢复到对照水平。毒素处理后 90 分钟，富含胆小管复合物的肝细胞膜的脂质成分没有显示出显着变化，但在 24 小时时，磷脂含量上升，膜流动性增加。这些结果清楚地表明，单次低剂量鬼笔环肽后的胆汁流量变化可以与特定的细管周围微丝分布分离，进一步支持正常胆道功能并不严格依赖于肌动蛋白丝网络的完整性的观点。
To study the relationship between the dynamic actin web and bile secretion, we developed an acute model of cholestasis, using phalloidin, and examined sequential morphologic and biochemical events in rat liver. Biliary function (bite flow, bile, and canalicular membrane components) and cellular integrity (release of hepatic enzymes in serum and bile, canalicular structure, and microfilaments distribution) in rats given a single iv dose of phalloidin (0.8 mg/kg body weight) were assessed at 15, 45, and 90 min, 24 hr, and 5 days postinjection. Bile flow decreased significantly at 45 and 90 min, but cholestasis was transient since bile secretion returned to control levels at 24 hr. The biliary bile acid secretion rate was not modified during the same time period, indicating that cholestasis may have been due to impairment of the bile acid independent component of bile flow. Serum alanine aminotransferase and lactate dehydrogenase as well as biliary alkaline phosphatase and alkaline phosphodiesterase-1 activities were not altered by phalloidin treatment. These data, coupled with morphologic studies, provide no evidence of cell damage. Electron microscopy revealed that the pericanalicular actin web in both centrilobular and periportal hepatocytes was increased at 90 min and further enlarged at 24 hr and 5 days after phalloidin injection. At all time periods, the canalicular structure was well preserved. Na+K+ -ATPase and Mg2+ -ATPase activities in membrane fractions enriched in bile canalicular complexes decreased significantly at 15 min and remained low up to Day 5. Mg2+ -ATPase activity returned to control levels by Day 5. The lipid constituents of liver cell membranes enriched in canalicular complexes showed no significant variations 90 min after toxin treatment but, at 24 hr, phospholipid content rose and membrane fluidity increased. These results clearly indicate that the bile flow variation after a single low dose of phalloidin can be dissociated from specific pericanalicular microfilament distribution, lending further support to the view that normal biliary function is not strictly dependent on the integrity of the actin filament network.