Bendahan J, Tyler M, Lotz Z, McLeod H, Engelbrecht G H, Kahn D, Hickman R
Department of Surgery, University of Cape Town, South Africa.
Transplantation. 1994 Mar 15;57(5):655-8. doi: 10.1097/00007890-199403150-00003.
It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate amino-transferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.
先前的研究表明，如果大鼠肝脏在部分肝切除术后同时遭受缺血、冷溶液冲洗或移植，肝脏再生会延迟。我们最近发现，术前用环孢素A（CsA）治疗可克服冲洗的抑制作用，并使再生反应恢复到正常时间范围。本研究旨在调查给予他克莫司（FK506）是否也能使观察到的延迟再生反应恢复正常。对体重250 - 350克的Long - Evans大鼠进行标准的68%部分肝切除术。第1组不进行进一步治疗；第2组，用10毫升冷（4℃）乳酸林格氏液冲洗肝脏残端；第3组，在部分肝切除术和冲洗（同第2组）前3天，通过肌肉注射给予FK506（1毫克/千克/天），共3天；在手术操作完成后给予最后一剂。每组每6只动物为一组，在术后4、24、48、72和96小时处死，采集血样测定血浆天冬氨酸氨基转移酶。对肝活检组织进行分析，以测定胸苷激酶和鸟氨酸脱羧酶活性，并计数有丝分裂细胞数。虽然第1组在24小时时记录到的胸苷激酶活性最高，但第2组和第3组均延迟至48小时，且第3组在96小时时计数仍保持较高水平。有丝分裂指数仅在96小时时显著升高（与第1组相比），而鸟氨酸脱羧酶活性与这些变化无关，在4小时时显著低于第2组和第3组，在24小时时第3组也显著低于其他两组。第3组的血浆天冬氨酸氨基转移酶也显著更高。结论是，对接受部分肝切除术和冲洗的大鼠术前给予FK506并不能使延迟的再生反应恢复正常，而是增强了反应（以胸苷激酶衡量，但不以有丝分裂指数衡量），该反应在48小时开始，96小时时仍然存在。
