犬部分肝切除对三甲双酮代谢及微粒体单加氧酶的影响。

Tanaka E, Osada A, Ishikawa A, Nakamura T, Momose Y, Mikami T, Fukao K, Horie T

Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan.

Xenobiotica. 1995 Dec;25(12):1301-10. doi: 10.3109/00498259509061919.

The recovery of trimethadione (TMO) metabolism and its association with liver weight and the activity of TMO N-demethylase have been reported in rat following partial (68%) hepatectomy. In the present study, we examined the effect of liver regeneration on hepatic P450 isozymes and TMO metabolism in dog. 2. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO at 2 h after i.v. injection of TMO (4 mg/kg) fell to 80% of that in the preoperative animals by 24 h after hepatectomy. The DMO/TMO ratio gradually recovered from days 7 to 14, and by day 21 after hepatectomy it had increased to about 25%. At 28 days post-hepatectomy the ratio had returned to preoperative levels. 3. The activity of benzphetamine N-demethylase, TMO N-demethylase, p-nitro-anisole O-demethylase and aniline hydroxylase increased 3 days post-hepatectomy, exhibiting levels 4.77, 3.45, 1.51 and 1.91 times greater respectively than that of the preoperative liver in the same animal. Two weeks post-hepatectomy these activities had returned to normal. The activity of the 16 beta- and 2 beta-hydroxylation of testosterone was unchanged. However, the activity of 6 beta-hydroxylase decreased 7 days post-hepatectomy, while 16 alpha-hydroxylation had increased at 3 and 7 days post-hepatectomy compared with controls. 4. The changes in liver weight were nearly restored to preoperative levels 7 days post-hepatectomy. 5. Although the P450 content was unchanged from days 1 to 7 post-hepatectomy, it had decreased by 30% at day 14 and by 20% at day 28. The P4502B11 content 3, 7 and 14 days post-hepatectomy had increased 8, 10 and 2 times respectively, while the P4503A12 content at 7 and 14 days decreased by 30 approximately 50% compared with that of the pre-operative liver. 6. The data presented above do not reveal any relationship between P4502B11 induction and liver regeneration. The reason for such a change is unknown, therefore further investigation needs to be carried out.

部分肝切除（68%）后大鼠体内三甲双酮（TMO）代谢的恢复及其与肝脏重量和TMO N-脱甲基酶活性的关系已有报道。在本研究中，我们检测了肝脏再生对犬肝脏P450同工酶及TMO代谢的影响。2. 静脉注射TMO（4mg/kg）后2小时，作为TMO唯一代谢产物的二甲双酮（DMO）与TMO的比值，在肝切除术后24小时降至术前动物的80%。DMO/TMO比值在肝切除术后第7天至第14天逐渐恢复，到第21天时已增至约25%。肝切除术后28天，该比值恢复到术前水平。3. 苯丙胺N-脱甲基酶、TMO N-脱甲基酶、对硝基苯甲醚O-脱甲基酶和苯胺羟化酶的活性在肝切除术后3天增加，分别比同一动物术前肝脏的活性高4.77、3.45、1.51和1.91倍。肝切除术后两周，这些活性恢复正常。睾酮16β-和2β-羟化的活性未改变。然而，6β-羟化酶的活性在肝切除术后7天降低，而与对照组相比，16α-羟化在肝切除术后3天和7天增加。4. 肝切除术后7天，肝脏重量的变化几乎恢复到术前水平。5. 虽然肝切除术后第1天至第7天P450含量未变，但在第14天降低了30%，在第28天降低了20%。肝切除术后3天、7天和14天，P4502B11含量分别增加了8倍、10倍和2倍，而与术前肝脏相比，P4503A12含量在7天和14天时降低了约30%至50%。6. 上述数据未揭示P4502B11诱导与肝脏再生之间的任何关系。这种变化的原因尚不清楚，因此需要进一步研究。