FK506对肝脏保存再灌注中肝窦内皮细胞损伤的保护作用

Preventive effect of tacrolimus(FK506)on sinusoidal endothelial cell injury during hepatic preservation and reperfusion

目的 探讨他克莫司 (FK5 0 6 )对肝脏低温保存再灌注中肝窦内皮细胞损伤的保护作用。方法 应用离体大鼠肝脏保存再灌注模型 ,测定保存不同时间后肝脏灌注流出液中内皮素 (ET)及丙氨酸转氨酶 (ALT)的含量以及透明质酸 (HA)的摄取量 ,光镜及电镜下观察肝窦内皮细胞的形态学改变 ,比较分析FK5 0 6对上述指标的影响。结果 对照组随肝脏保存再灌注时间延长 ,灌注流出液中ET含量明显升高 (P <0 .0 5 ) ,HA摄取量明显降低 (P <0 .0 5 ) ,并伴随ALT活性显著增高 (P <0 .0 5 )和肝窦内皮细胞形态学的异常改变 ;保存液和灌注液中均加入FK5 0 6后 ,上述指标异常变化均明显减轻 ,其差异有显著性 (P <0 .0 5 )。结论 FK5 0

Objective To investigate the structural and functional changes in sinusoidal endothelial cells (SEC) during hepatic preservation and reperfusion and protective effect of tacrolimus (FK506). Methods The changes in endothelin (ET) content, hyaluronic acid (HA) uptake, alanine aminotransferase (ALT) activity and morphological changes in hepotocytes and SEC under light microscopy and electron microscopy were observed by using isolaec perfused rat liver model. The effect of FK506 on the above parameters were also observed. Results In the control group with prolongation of liver preservation and reperfusion, ET content and ALT activity were increased remarkably (both P < 0.05 ), and abnomal morphological changes of hepatocytes and SEC were obvious. With the treatment of FK506, the abnormal changes of all the above parameters were improved remarkably ( P < 0.05 ). Conclusions SEC injury may be the main causes of microcirculation disturbance and graft failure following reperfusion. FK506 could prevent the isolated SEC from injury during hepatic preservation and reperfusion.