Tamura F, Masuhara A, Sakaida I, Fukumoto E, Nakamura T, Okita K
First Department of Internal Medicine, Yamaguchi University, School of Medicine, Japan.
J Gastroenterol Hepatol. 1998 Jul;13(7):703-8. doi: 10.1111/j.1440-1746.1998.tb00717.x.
We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-beta 1 (TGF-beta 1) and found no changes in HGF and TGF-beta 1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.
我们研究了强效免疫抑制剂水合他克莫司（FK506）在部分肝切除术后促进肝脏再生的机制。与安慰剂组相比，在70%肝切除术后36小时和48小时，给予FK506显著增加了溴脱氧尿苷（BrdU）标记指数。使用相同模型，我们研究了FK506对肝细胞生长因子（HGF）和转化生长因子-β1（TGF-β1）表达的影响，发现肝脏中HGF和TGF-β1 mRNA表达以及血浆中HGF蛋白浓度均无变化。我们发现，在部分肝切除时，用FK506预处理可显著降低肝脏驻留自然杀伤（NK）细胞的活性和数量。我们的观察结果表明，FK506促进肝脏再生可能归因于肝脏驻留NK细胞数量的减少及其活性的抑制。
