Xu D, Sorrell M F, Casey C A, Tuma D J
Liver Study Unit, Department of Veterans Affairs Medical Center, Omaha, Nebraska.
Lab Invest. 1992 Aug;67(2):186-90.
Previous studies have shown that the assembly and properties of the hepatocyte plasma membrane are altered by ethanol administration, indicating possible changes in the receptor-mediated binding of the plasma membrane to extracellular matrix substrates. In the present study, the effects of chronic ethanol consumption on the ability of hepatocytes to attach to various components of the extracellular matrix were investigated.
Rats were pair-fed for 5 weeks with a liquid diet containing either ethanol (as 36% of total calories) or isocaloric carbohydrate. The effects of ethanol treatment on hepatocyte-extracellular matrix interactions was ascertained by determining the ability of isolated hepatocytes to attach to various extracellular matrix substrates.
The attachment of hepatocytes, isolated from the ethanol-fed rats, to laminin-coated plates was significantly decreased compared with hepatocytes from chow-fed or pair-fed controls. Greater decreases in attachment were seen when higher numbers of hepatocytes were seeded in the plates. Similar inhibitions of attachment were also observed when fibronectin or type I collagen were used as matrices. Time-course cell attachment assays indicated that the maximum extent of attachment rather than the rate of attachment was primarily altered by chronic ethanol feeding. Hepatocytes from the ethanol-fed rats also detached more readily from the matrix-coated plates than those from the controls. A reduced number of functional surface receptors for matrix components is likely the most important factor that accounts for the ethanol-induced impairment of hepatocyte attachment.
These results indicate that chronic ethanol administration impairs the interactions of hepatocytes with their extracellular matrix and that this defect could lead to alterations of hepatocyte structure and function.
先前的研究表明，乙醇给药会改变肝细胞质膜的组装和特性，这表明质膜与细胞外基质底物的受体介导结合可能发生变化。在本研究中，研究了长期摄入乙醇对肝细胞附着于细胞外基质各种成分能力的影响。
将大鼠用含乙醇（占总热量的36%）或等热量碳水化合物的液体饲料配对喂养5周。通过测定分离的肝细胞附着于各种细胞外基质底物的能力，确定乙醇处理对肝细胞 - 细胞外基质相互作用的影响。
与正常饮食或配对喂养对照组的肝细胞相比，从乙醇喂养大鼠分离的肝细胞对层粘连蛋白包被平板的附着显著降低。当在平板中接种更多数量的肝细胞时，附着的降低更为明显。当使用纤连蛋白或I型胶原作为基质时，也观察到类似的附着抑制。时间进程细胞附着试验表明，长期乙醇喂养主要改变的是附着的最大程度而非附着速率。与对照组相比，乙醇喂养大鼠的肝细胞也更容易从基质包被的平板上脱离。基质成分功能性表面受体数量减少可能是乙醇诱导肝细胞附着受损的最重要因素。
这些结果表明，长期给予乙醇会损害肝细胞与其细胞外基质的相互作用，这种缺陷可能导致肝细胞结构和功能的改变。
