Kitano H, Fukui H, Okamoto Y, Kikuchi E, Matsumoto M, Kikukawa M, Morimura M, Tsujita S, Nagamoto I, Nakatani T, Takaya A, Tsujii T
Third Department of Internal Medicine, Nara Medical University, Japan.
Alcohol Clin Exp Res. 1996 Feb;20(1 Suppl):73A-76A. doi: 10.1111/j.1530-0277.1996.tb01735.x.
In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL- bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.
在本研究中，探讨了白蛋白和高密度脂蛋白（HDL）作为内毒素（Et）结合蛋白在长期酒精喂养大鼠中的作用。在急性乙醇负荷大鼠中，血液中Et清除略有延长，血液中与白蛋白和HDL结合的Et量显著增加。在慢性乙醇负荷大鼠中，Et清除明显快于对照组，且与HDL结合的Et增加。在额外给予5 g/kg体重乙醇负荷的慢性乙醇喂养大鼠中，当与HDL结合的Et未进一步增加时，Et清除显著延长，血液肿瘤坏死因子和ALT升高。当库普弗细胞在含乙醇的培养基中预孵育，然后将所得培养上清液加入肝细胞培养系统时，肝细胞培养基中总蛋白、白蛋白和HDL的Et结合能力增加。在慢性乙醇负荷大鼠的培养实验中，未观察到这种增加。这些结果表明，HDL和白蛋白的Et结合能力增加可能是慢性乙醇负荷大鼠对抗Et的一种保护机制。给这些大鼠添加高剂量乙醇可能导致Et结合和失活受损，最终可能导致内毒素血症增加。
