他克莫司对大鼠减体积肝移植后肝再生的影响

Effects of tacrolimus on liver regeneration after reduced-size liver transplantation in rats

目的:观察他克莫司对大鼠减体积肝移植后肝再生的影响。方法:建立大鼠部分肝(65％)移植模型,并随机分为对照组、他克莫司大剂量组(0.1 mg·kg-1·d-1)和他克莫司小剂量组(0.05mg·kg-1·d-1),每组各24只。受体于术前3 d起肌注给药,每天1次,直至术后。观察术后第1、2、3、5天肝细胞有丝分裂指数(MI)、增殖细胞核抗原标记指数(PCNA LI),速率法检测血清胆红素(TB)、谷丙转氨酶(ALT)等指标。结果:肝移植术后的肝细胞有丝分裂的高峰期出现在术后48 h,他克莫司显著提高了大鼠减体积肝移植术后48 h MI及PCNA LI(P<0.05,P<0.01);大剂量实验组术后48 h PCNA LI高于小剂量组(P<0.05);两种剂量组的TB、ALT没有明显改变。结论:他克莫司对大鼠减体积肝移植后肝再生有促进作用,且该作用有剂量依赖性,同时肝脏毒性较小。

Objective:To study the effects of tacrolimus on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation in rats. Methods: Wistar rats, weighing 300-350 g, were subjected to 65% partial hepatic transplantation. Group A had no further treatment; group B and group C received tacrolimus(0. 1 and 0. 05 mg · kg-1 · d-1 respectively) through intramuscular injection from 3 d before the operation until the animals were killed 24, 48, 72, and 120 h after surgery. Blood samples were taken for measurements of plasma ALT and TB. Liver biopsies were analyzed for determination of mitotic index. Results: Tacrolimus significantly augmented proliferating cell nuclear antigen (PCNA) labeling index and mitotic index of hepatocytes after transplantation(P<0. 05,P<0. 01), and reached their peak 48 h after transplantation. The increase of PCNA labeling index in group B was greater than that in group C 48 h after operation(P<0. 05). No significant differences of serum ALT and TB levels were observed between group B and group C. Conclusion : Tacrolimus can dose-de pendantly augment liver regeneration after reduced-size hepatic transplantation in rats with low hepatotoxicity.