ALCOHOL-CONSUMPTION IN RATS POTENTIATES THE DELETERIOUS EFFECT OF GRAM-NEGATIVE SEPSIS ON HEPATIC HYALURONAN UPTAKE
ALCOHOL-CONSUMPTION IN RATS POTENTIATES THE DELETERIOUS EFFECT OF GRAM-NEGATIVE SEPSIS ON HEPATIC HYALURONAN UPTAKE
复制标题
DOI：
10.1111/j.1530-0277.1993.tb05655.x
复制
发表时间：
1993-10-01
影响因子：
3.2
通讯作者：
SPITZER, JJ
中科院分区：
文献类型：
--
作者：
DEACIUC, IV;MCDONOUGH, KH;SPITZER, JJ
肝窦内皮细胞(SECs)在与饮酒相关的肝脏病理变化中的作用尚不完全清楚。SECS对透明质酸(HA)摄取的测量为评估这些细胞的功能状态提供了有用的手段。在这项研究中，我们确定了在没有和存在皮下大肠杆菌诱导的脓毒症的情况下，急性和长期酒精暴露对大鼠血浆HA浓度和离体、灌流肝脏对HA摄取的影响。大鼠在处死前24小时和15小时给予乙醇(两次剂量为0.2g/100g体重)或含有酒精(占总热量的36%)或糊精(等卡路里)的流食8-10周。在实施肝脏灌流安乐死前21小时，动物皮下注射活的大肠杆菌(败血症)或无菌生理盐水(对照组)。急性或慢性酒精暴露本身都不会改变血浆HA水平。然而，这两种治疗方法都加剧了脓毒症的高透明质酸血症效应。因此，在急性酒精治疗的大鼠中，脓毒症导致血浆HA水平增加187%(p<；0.05)，而在非酒精脓毒症大鼠中，这一增加仅为54%(p<；0.05)。同样，脓毒症导致酒精喂养的大鼠血浆HA水平(871%)比液体饮食对照组大鼠(323%，p<；0.05)的增加更大。无论是急性还是慢性酒精暴露，隔离的灌流肝脏摄取HA的速率都不会改变。然而，酒精暴露明显增强了脓毒症对肝脏吸收HA能力的抑制作用。因此，在急性酒精处理的大鼠中，脓毒症降低了HA摄取量(60-80%，p<；0.05)，而在相应的非酒精对照组中，这种下降只有在HA输注开始时才明显。在慢性酒精喂养的大鼠中，脓毒症诱导了80%(p<；0.05)的HA摄取抑制，而在饮食喂养的对照组大鼠中，这种抑制只有60%(p<；0.05)。败血症抑制了隔离的、灌流的肝脏对HA摄取的抑制，这为以前在败血症的人和动物中观察到的高透明质酸血症提供了一个解释。由于酒精本身不会改变HA的代谢，结果表明，急性和慢性酒精暴露影响肝细胞之间的通讯，导致SECS下调HA清除。
The role of hepatic sinusoidal endothelial cells (SECs) in the pathologic changes of the liver associated with alcohol consumption is not fully understood. The measurement of hyaluronan (HA) uptake by the SECs provides a useful means for assessing the functional state of these cells. In this study, we determined the effect of acute and chronic exposure to alcohol in rats in the absence and presence of subcutaneous Escherichia coli-induced sepsis on plasma HA concentration and HA uptake by the isolated, perfused liver. Rats were administered ethanol (two doses of 0.2 g/100 g body weight, intraperitoneally, 24 and 15 hr before killing) or fed a liquid diet for 8-10 weeks, containing alcohol (36% of the total calories) or dextrin (in isocaloric amounts). Twenty-one hr before euthanizing for liver perfusion, animals were injected subcutaneously with live E. coli (sepsis) or sterile saline (control). Neither acute nor chronic alcohol exposure by themselves altered plasma HA levels. However, both treatments exacerbated the hyperhyaluronanemic effect of sepsis. Thus, in acutely alcohol-treated rats, sepsis induced a 187% (p < 0.05) increase in plasma levels of HA, whereas in nonalcohol septic rats, the increase was only 54% (p < 0.05). Likewise, sepsis resulted in a greater increase in the plasma levels of HA (871%) in alcohol-fed rats than it did in liquid diet, control-fed rats (323%, p < 0.05). The rate of HA uptake by the isolated, perfused liver was not altered by either acute or chronic alcohol exposure. However, alcohol exposure markedly potentiated the inhibitory effect of sepsis on the capacity of the liver to take up HA. Thus, in acutely alcohol-treated rats, sepsis decreased HA uptake (60-80%, p < 0.05), whereas in the corresponding nonalcoholic control group the decrease was evident only st the beginning of HA infusion. In chronically alcohol-fed rats, sepsis induced an 80% (p < 0.05) inhibition of HA uptake, whereas in diet-fed control rats the inhibition was only 60% (p < 0.05). The inhibition by sepsis of HA uptake by the isolated, perfused liver provides an explanation for the previously observed hyperhyaluronanemia in septic humans and animals. Because alcohol alone does not alter HA metabolism, the results suggest that acute and chronic alcohol exposure influences the communication between liver cells leading to downregulation of HA clearance by SECs.