Microfilament dysfunction as a possible cause of intrahepatic cholestasis.

Microfilament dysfunction as a possible cause of intrahepatic cholestasis.
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微丝功能障碍可能是肝内胆汁淤积的原因。

DOI:
10.1016/s0016-5085(19)32635-6
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发表时间:
1975
期刊:
影响因子:
29.4
通讯作者:
K. Jeejeebhoy
K. Jeejeebhoy
中科院分区:
医学1区
文献类型:
--
作者:
M. J. Phillips;M. Oda;E. Mak;M. M. Fisher;K. Jeejeebhoy

文献摘要

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观察细胞松弛素B对胆管结构和功能的影响。使用三种实验模型,培养的肝细胞,离体灌注肝,和体内输注肝。所使用的技术是光镜和电子显微镜,并在选定的情况下,扫描电子显微镜,电子“染色”的微丝,并测量胆汁流量。在体外和体内输注动物中,一致发现微丝断裂和胆小管扩张,并与胆汁流量减少密切相关。有人提出,在正常情况下,微丝维持小管处于收缩或部分收缩状态。因此,微丝网络将为小管系统提供张力,这将倾向于减少停滞并促进胆汁的流动。正如所观察到的,正常微丝收缩功能的去除预计会产生小管扩张和胆汁流量减少。因此,微丝功能障碍可能是肝内胆汁淤积的一个可能原因。这一假说的关键是在小管周网中存在含肌动蛋白的微丝,以及细胞松弛素B对它们的收缩性的作用。有关这些要求的证据进行了介绍和讨论。
The effects of cytochalasin Β on bile canalicular structure and function were examined. Three experimental models were used, cultured hepatocytes, isolated perfused liver, and in vivo infused liver. The techniques used were light and electron microscopy and, in selected instances, scanning electron microscopy, electron "stains" for microfilaments, and measurements of bile flow. Microfilament disruption and dilation of bile canaliculi were consistently found and closely paralleled a reduction in bile flow in both in vitro and in vivo infused animals. It is proposed that under normal circumstances, the microfilaments maintain the canaliculi in a contracted or partly contracted state. Hence, the microfilamentous network would provide tone to the canalicular system which would tend to reduce stagnation and facilitate the flow of bile. Removal of normal microfilament contractile function would be expected to produce canalicular ectasia and reduction of bile flow, as was observed. Microfilament dysfunction may therefore be a possible cause of intrahepatic cholestasis. Crucial to this hypothesis are the presence of actin-containing microfilaments in the pericanalicular web, and an action of cytochalasin Β on their contractility. Evidence pertaining to these requirements is presented and discussed.