脑死亡对大鼠肝移植后早期移植肝损伤的影响

Influence of brain death of donors on the injury of rat transplanted livers at the early stage after transplantation

目的探讨脑死亡状态对大鼠供肝肝移植后早期肝脏损伤的影响。方法Wistar大鼠80只随机分为活体大鼠供肝肝移植组(L组)和脑死亡大鼠供肝肝移植组(B组)。L组仅建立活体大鼠供肝的二袖套法原位肝移植模型,B组供体大鼠建立脑死亡模型后切取供肝行二袖套法原位肝移植。监测脑死亡模型建立过程中大鼠血压和心率变化,观察肝移植术后受体6h、24h存活率,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、透明质酸(HA)和肿瘤坏死因子-α(TNF-α)水平,电镜观察肝脏形态变化,TUNEL法测定肝组织细胞凋亡情况。结果B组供体大鼠脑死亡模型建立后血压和心率与L组比较,差异有统计学意义(P=0.001)。L组和B组6h和24h生存率差异无统计学意义(P>0.05)。与L组比较,B组ALT、AST、TNF-α和HA水平均升高(P<0.05),肝细胞形态学损伤重、凋亡率高(P<0.05)、Kupffer细胞显著活化。结论供体脑死亡可以加重脑死亡供肝移植后早期肝脏损伤,其机制可能和脑死亡供体血压、心率的改变以及Kupffer细胞的活化有关。

Aim ： To evaluate the influence of brain death of donors on the liver injury at the early stage after transplantation, Methods：A total of 80 Wistar rats were randomly allocated into living donor group （L） and brain-dead donor （BDD） group （B）, in which brain-dead models were established in the donors and then liver transplantation was performed using microsurgical techniques as group L. Heart rate and blood pressure of BDD were monitored. Survival rates were recorded and serum alanine aminotransferase （ALT） , aspartate aminotransferase （AST） , tumor necrosis factor alpha （TNF-α） , and hyaluronic acid （HA） were determined during 24 h after transplantation. Graft samples were fixed for morphological observation and the apoptosis of hepatoeytes were detected using TUNEL method. Results： Heart rate and blood pressure of BDD for group B during the whole experiment showed significant changes （ P =0. 001 ）. Survival rates showed no significant difference between group L and B （P 〉 0. 05）. Serum levels of ALT, AST, TNF-α, and HA in group B were significantly higher than those in group L after transplantation （ P 〈 0. 05 ）. Electron microscopy showed that Kupffer ceils activated more obviously, apuptotie rate was higher （ P 〈 0. 05 ）, and hepatocytes injured more severely in group B compared with group L. Conclusion： Brain death of donors can aggravate liver injury at the early stage after transplantation, which may be related with the changes of the heart rate and blood pressure and the activation of Kupffer ceils.