Yokoi T, Nagayama S, Kajiwara R, Kawaguchi Y, Aizawa T, Otaki Y, Aburada M, Kamataki T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Toxicol Lett. 1995 Feb;76(1):33-8. doi: 10.1016/0378-4274(94)03190-8.
Long Evans Cinnamon (LEC) rats, that spontaneously develop hepatitis, were found to possess autoantibodies to liver microsomal proteins (anti-LM) before the development of hepatitis. Anti-LM antibody was assumed to appear in association with the lethal hepatitis in the LEC rats. Thus, the purpose of this study was to investigate the effects of an anti-hepatitis drug on the development of hepatitis and the occurrence of the antibody in LEC rats. Mortality, blood biochemical parameters and the titer of serum anti-LM antibody were measured. In control LEC rats, 4 of 8 rats died before 20 weeks of age. In rats treated with TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11 - methylenedioxy-6-dibenzo[a,c]cyclooctenol), 4 of 7 rats died of hepatitis, but the time of death was delayed by 7-10 weeks compared to the control rats. The titer of the anti-LM antibody increased 3-7 weeks before death in the non-survivors in control and TJN-101-treated rats, supporting the idea that anti-LM antibody occurs in association with acute lethal hepatitis.
长 Evans 肉桂色（LEC）大鼠会自发患上肝炎，研究发现它们在肝炎发病前就已拥有针对肝脏微粒体蛋白的自身抗体（抗 LM）。抗 LM 抗体被认为与 LEC 大鼠的致死性肝炎有关。因此，本研究的目的是调查一种抗肝炎药物对 LEC 大鼠肝炎发展及抗体产生的影响。测定了死亡率、血液生化参数以及血清抗 LM 抗体的滴度。在对照 LEC 大鼠中，8只大鼠中有4只在20周龄前死亡。在用TJN - 101（(+)-(6S,7S,R - biar)-5,6,7,8 - 四氢 - 1,2,3,12 - 四甲氧基 - 6,7 - 二甲基 - 10,11 - 亚甲基二氧基 - 6 - 二苯并[a,c]环辛烯醇）治疗的大鼠中，7只大鼠中有4只死于肝炎，但与对照大鼠相比，死亡时间延迟了7 - 10周。在对照和 TJN - 101 治疗的大鼠中，非存活者在死亡前3 - 7周抗 LM 抗体滴度升高，这支持了抗 LM抗体与急性致死性肝炎有关的观点。
