多烯磷脂酰胆碱对大鼠移植肝缺血再灌注损伤的保护作用

Polyene phosphatidylcholine in the prevention of ischemia related biliary tract injury in rat＇s Hver transplantation

目的探讨多烯磷脂酰胆碱对大鼠肝移植术中相对热缺血（relative warm ischemia time，RWIT）造成胆道损伤的保护作用。方法将60只SD大鼠分为胆道相对热缺血0min（A组）、胆道相对热缺血60min（B组）、胆道相对热缺血60min并于术后每日腹腔注射多烯磷脂酰胆碱注射液（c组）。建立大鼠自体原位肝移植胆道外引流模型，检测各组术后2h及术后第1、3、5天胆汁中总胆汁酸（total bilirubin，TBA）浓度、磷脂（phospholipid，PL）浓度、TBA／PL值，并留取胆道标本进行组织病理学检测，并检测胆汁碱性磷酸酶（alkaline phosphatase，ALP）及谷氨酰基转移酶（gamma glutamyltrans南mse，γ-GT）水平作为观察胆管损伤的指标。结果A组术后TBA、PL及TBA／PL均稳定，未出现明显变化；TBA浓度：术后早期B、C组明显低于A组（F=19．662，P〈0．05），此后逐渐升高，到第3天各组之间已无明显差异（F=1．244，P〉0．05）。PL浓度：术后B组较C组下降明显，此后缓慢升高，至术后第5天仍低于C组（t=2．832，P〈0．05）。TBA／PL值：术后早期B组明显高于A组，并于术后逐渐升高，至术后第3天达到最高，术后第5天开始下降。C组术后未出现明显变化，在各个时间点A、C组之间比较差异无统计学意义（f=0．307，P〉0．05）。胆道损伤评分（胆汁ALP水平、γ-GT水平、胆道病理形态学评分、线粒体平均体积及胆道上皮细胞微绒毛密度）组间两两比较差异有统计学意义，A组（对照组）大致正常，B组（相对热缺血组）最重，C组（干预组）较轻。结论胆道相对热缺血再灌注损伤使肝移植术后早期分泌的胆汁中胆盐及磷脂分泌均降低，其中胆盐早期恢复分泌，而磷脂恢复分泌较迟，导致了早期TBA／PL值增高，胆汁毒性增强，是导致胆道损伤的因素之一；多烯磷脂酰胆碱注射液可增加胆汁中磷脂浓度，并降低TBA／PL值，减少胆汁毒性，减轻因相对热缺血导致的胆道损伤。

Objective ＂To investigate the preventive effects of polyene phosphatidylcholine on biliary tract injury induced by relative warm isehemia time （RWIT） in liver transplantation in rats. Methods Sixty SD rats were divided into three groups. The RWIT was 0 min for group A and 60 min for group B and C, and in group C polyene phosphatidylcholine was given intraperitoneally beginning 6 hrs before and QD postoperatively until the day the graft was harvested. Total bilirubin （TBA）, phospholipid （PL） and TBA/PL was detected at 2 hours and 1st, 3rd,5th day after operation. Histopathology, ALP and γ-GT were used to evaluate biliary tract damage. Results The levels of total bilirubin （TBA）, phospholipid（PL） and TBA/PL were stable in group A; The levels of TBA： group B and C were lower than group A significantly in the early stage after operation （ P 〈 0.05 ） and increased gradually. There was no significant differences between three groups on the 3rd day. The levels of PL in group B were much lower than those in group C on the 5th day（P 〈 0.05 ）. TBA/PL ratio in group B was significantly higher than that in group A（P 〈0. 05）. TBA/PL in group C was stable and there were no significant differences between group A and group C. Compared with that of group B the injury of liver cells and biliary duct were significantly ameliorated in group C. Conclusion The RWIT in liver transplantation caused imbalanced bile salt and phospholipid secretion, resulting in an elevated TBA/PL ratio leaving the bile duct to bile salt toxicity. When polyene phosphatidylcholine was given, it increased the concentration PL and decrease the value of TBA/PL , attenuating bile toxicity and alleviating bilary duct injury caused by RWIT.