Significance of Acetaldehyde-Protein Adducts in Patients With Alcoholic Hepatitis

酒精性肝炎的特征是酒精滥用引起的急性肝脏炎性病变，但酒精滥用诱导肝脏炎症的机制尚不清楚。最近，化学惰性外来物质在肝脏中被代谢活化，与肝脏大分子联合收割机结合，从而引起肝损伤的概念被用来解释许多药物的肝毒性。众所周知，乙醛也是醇（乙醇）氧化的活性代谢产物。因此，乙醛可以共价结合到肝细胞大分子，从而改变肝细胞的结构和功能。为了测试这一点，通过SD大鼠的门静脉灌注乙醛（100 μ M）60分钟而不进行再循环，并使用氚化氰基硼氢化钠在体外测定乙醛加合物与灌注大鼠的分离肝细胞的形成。氚的掺入被发现是可检测的， ...更多信息 鲸蜡醇处理的肝细胞。然后，为了测试对乙酰丙酮化物处理的大鼠肝细胞的免疫反应，将酒精性肝炎患者的血清与分离的肝细胞孵育，并测定加合物的血清抗体。结果，12例酒精性肝炎患者中有10例血清抗体阳性，而31例非酒精性肝病患者血清抗体均为阴性。为研究乙醛加合物对细胞毒性T细胞的作用，将酒精性和非酒精性肝病患者的淋巴细胞与乙醛共同孵育，一部分作为刺激细胞，另一部分经Cr标记后作为靶细胞。用刺激细胞激活的淋巴细胞与靶细胞共同培养，18例酒精性肝病患者中有5例检测到淋巴细胞毒性。14例非酒精性肝病患者未发现细胞毒性。所有这些结果表明，淋巴细胞毒性反应的乙酰丙酮酸-蛋白加合物是，至少部分，发挥作用的炎症反应引起的酒精滥用。少

Alcoholic hepatitis is characterized by acute inflammatory lesion of the liver caused by alcohol abuse, but the mechanism by which alcohol abuse induces hepatic inflammation is not known. Recently, the concept that chemically inert foreign substances are metabolically activated in the liver, combine with hepatic macromolecules and thereby cause liver injury has been invoked to explain the hepatotoxicity of a number of drugs. It is well-known that acetaldehyde is also an active metabolite of alcogol (ethanol) oxidation. Thus, acetaldehyde is possible to covalently bind to hepatocellular macromoecules and thereby alter hepatocellular structure and function. To test this, acetaldehyde (100uM) was perfused through the portal vein of SD rats for 60 min without recirculation and the formation of acetaldehyde adducts to isolated hepatocytes of the perfused rats was determined in vitro using tritiated sodium cyanoborohydride. The incorporation of the tritium was found to be detectable in the a … More cetaldehyde-treated hepatocytes. Then, to test an immunological reaction against the acetaldehyde-treated rat hepatocytes, sera from patients with alcoholic hepatitis were incubated with the isolated hepatocytes and serum antibodies to the adducts were determined. As a result, serum antibodies were found to be positive in 10 of 12 patients with alcoholic hepatitis, whereas they were negative in all 31 patients with non-alcoholic liver disease. In order to study cytotoxic T-cell response to acetaldehyde adducts, lymphocytes taken from patients with alcoholic and non-alcoholic liver diseases were incubated with acetaldehyde, and one part was used as stimulator cells and another as target cells after labeled with Cr. When lymphocytes activated with the stimulator cells were cultured with the target cells, lymphocyte cytotoxicity was detected in 5 of 18 patients with alcoholic liver disease. The cytotoxicity was not found in 14 patients with non-alcoholic liver disease. All these results suggest that lymphocytotoxic response to acetaldehyde-protein adducts is, at least in part, play a role for the inflammatory reaction caused by alcohol abuse. Less