前列腺素E_1对脑死亡大鼠供肝微循环的保护作用

Protective effect of prostaglandin E_1 on hepatic microcirculation in brain death rats

背景:脑死亡供者维护对于改善脑死亡供者器官质量具有重要意义,前列腺素E1被广泛使用于临床肝移植领域,但有关前列腺素E1对脑死亡供者的作用未见报道。目的:通过建立稳定的大鼠渐进性脑死亡模型,观察前列腺素E1对脑死亡供肝微循环的保护作用。方法:SD大鼠按随机数字表法分为3组,脑死亡组及前列腺素E1组建立渐进性脑死亡大鼠模型,前列腺素E1组于脑死亡诱导后,经尾静脉微输液泵通道以0.05μg/(kg·min)速度持续性泵入前列腺素E1注射液。各组在脑死亡诱导后的2,4h分别采血及获取肝脏标本。自动生化仪检测肝酶学指标天冬氨酸转氨酶、丙氨酸转氨酶活性,放射免疫分析法测定血清透明质酸质量浓度,日立H-600型透射电镜观察肝血窦超微结构变化。结果与结论:脑死亡诱导2h后,大鼠肝功能出现不同程度异常;诱导脑死亡4h后,脑死亡大鼠的肝功能损伤进一步加重,前列腺素E1组较脑死亡组有明显改善(P<0.05)。脑死亡诱导2h后,透明质酸质量浓度升高提示肝脏微循环障碍;诱导脑死亡4h后,脑死亡组大鼠的透明质酸质量浓度进一步升高,前列腺素E1组较脑死亡组有明显改善(P<0.05)。脑死亡后透射电镜显示肝细胞及肝窦内皮细胞的超微结构受损,Kupffer细胞活化,前列腺素E1可减轻大鼠肝脏超微结构的损伤并抑制Kupffer细胞活化。提示前列腺素E1能改善脑死亡大鼠的肝功能及肝脏微循环,抑制肝脏Kufpper细胞的活化可能是其作用机制之一。

BACKGROUND：Brain death donor management has an important role on protecting the function of organs.Prostaglandin E1（PGE1） is used widely in the filed of liver transplantation because of its effect on protecting the liver function,but its effect on the brain death donors and the grafts has not been illustrated.OBJECTIVE：To investigate the protective effect of PGE1 on hepatic microcirculation in brain death donor rats models.METHODS：Sprague-Dawley rats were inducted brain death by gradual on-set method.All rats were divided into 3 groups：brain death group,PGE1 group and contrast group.Blood and liver specimen were harvested at 2 and 4 hours after brain death induction.The activities of aspartate aminotransferase and alanine aminotransferase were detected by automatic biochemical analyzer,hyaluronic acid（HA） concentration was measured by radio immunoassay,and the ultrastructure changes of hepatic sinusoid were observed by Hitachi H-600 transmission electron microscope.RESULTS AND CONCLUSION：Hepatic function was dysfuncted at 2 hours after brain death,which aggravated at 4 hours.Liver enzymes in the PGE1 group were improved compared with the brain death group（P 0.05）.At 2 hours after brain death,HA levels were increased in the brain death group at 2 hours and continuous rose at 4 hours.After brain death,electron microscope showed the microstructure of the hepatocytes and sinusoids endothelial cells were damaged,Kupffer cells were activated.PGE1 management on the brain death donor can improve the microcirculation of liver,inhibit apoptosis of liver cells and activation of Kupffer cells,and then it can improve the quality of liver grafts from brain death donors.