Yokoi T, Nagayama S, Kajiwara R, Kawaguchi Y, Kamataki T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Res Commun Mol Pathol Pharmacol. 1994 Jul;85(1):73-81.
Long Evans Cinnamon (LEC) rats, which spontaneously develop hepatitis, produce an autoantibody to protein disulfide isomerase (PDI) before the development of clinical signs of hepatitis. Anti-PDI antibody may be associated with immunological hepatitis. Thus, the purpose of this study was to investigate the effects of some drugs on the development of hepatitis and the occurrence of the antibody in LEC rats. Cyclosporin-A, an immunosuppressant, and D-penicillamine, which promotes copper excretion, were orally administered to LEC rats for 23 weeks. Mortality, blood biochemical parameters and the titer of serum anti-PDI antibody were measured. In control LEC rats, four of eight rats died before 20-weeks-old. Only one of seven rats in the cyclosporin-A-treated group died at the age of 20 weeks. When rats were treated with D-penicillamine, the development of clinical signs of hepatitis was inhibited, and all rats survived. Cyclosporin-A-treated rats showed increases in blood biochemical parameters similar to those in control rats. The titer of anti-PDI antibody in control rats was higher the non-survivors than survivors. These findings suggest the association of the anti-PDI antibody with lethality, but not with the apparent development and progression of hepatitis as measured by blood biochemical parameters in LEC rats.
长 Evans 肉桂色（LEC）大鼠会自发发展为肝炎，在肝炎临床症状出现之前就会产生针对蛋白质二硫键异构酶（PDI）的自身抗体。抗 PDI 抗体可能与免疫性肝炎有关。因此，本研究的目的是调查某些药物对 LEC 大鼠肝炎发展及抗体产生的影响。将免疫抑制剂环孢素 A 和促进铜排泄的 D-青霉胺口服给予 LEC 大鼠 23 周。测量死亡率、血液生化参数和血清抗 PDI 抗体滴度。在对照 LEC 大鼠中，8 只大鼠中有 4 只在 20 周龄前死亡。环孢素 A 治疗组的 7 只大鼠中只有 1 只在 20 周龄时死亡。当用 D-青霉胺治疗大鼠时，肝炎临床症状的发展受到抑制，所有大鼠均存活。环孢素 A 治疗的大鼠血液生化参数升高，与对照大鼠相似。对照大鼠中抗 PDI 抗体滴度在非存活者中高于存活者。这些发现表明抗 PDI 抗体与致死率有关，但与 LEC 大鼠血液生化参数所衡量的肝炎明显发展和进展无关。
