Sakaguchi Y, Inaba S, Irita K, Sakai H, Nawata H, Takahashi S
Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Japan.
Can J Anaesth. 1994 May;41(5 Pt 1):398-403. doi: 10.1007/BF03009862.
It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with "halothane hepatitis (HH)," and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU.L-1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.
研究表明，在体内接触氟烷后获得的与大鼠肝微粒体蛋白结合的循环抗体，可通过免疫印迹法在“氟烷肝炎（HH）”患者中检测到，并且用抗三氟乙酰化兔血清白蛋白（TFA - RSA）免疫的兔抗血清识别大鼠微粒体扭曲多肽的方式与HH患者的血清几乎相同。在本文中，我们首先报告了一种使用对硝基苯基三氟乙酸合成TFA - RSA的新方法，其次报告了对86例接受氟烷麻醉且未发生（67例）或仅发生轻度（19例，血清丙氨酸氨基转移酶最高活性为519 IU.L-1）肝损伤患者血清中循环抗TFA抗体的检测结果。血清选自输血后患者的储存血清。合成TFA - RSA的新方法简便，且能在中性pH条件下进行。用新合成的TFA - RSA免疫后获得的兔血清识别与已建立的抗TFA - RSA血清相同的多肽（109 kDa、92 kDa、80 kDa、76 kDa、64 kDa和59 kDa），并且这些反应在TFA - 赖氨酸存在下受到抑制。在我们那些未发生或仅发生轻度肝损伤的患者中未检测到循环抗体。目前的发现支持了针对微粒体扭曲蛋白的循环抗体的出现是HH患者特有的这一假说。此外，我们在此表明，氟烷诱导的ALT活性轻度升高与那些循环抗体的出现无关，这支持了HH与氟烷诱导的轻度肝损伤之间的病理生理差异。
