肝缺血/再灌注损伤与高胆红素血症关系的研究

Relationship between liver ischemia/reperfusion injury and hyperbilirubinemia

目的:探讨大鼠肝缺血/再灌注(I/R)损伤致高胆红素血症发生的可能机制。方法:健康Wistar大鼠48只随机分为对照组、缺血30min组(I组)、缺血30min即刻再灌注组(I/R组)及I/R1、2、4h组共6组,每组8只,测定各组肝组织肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的含量及髓过氧化物酶(MPO)、黄嘌呤氧化酶(XO)、丙二醛(MDA)的活性和血清总胆红素(TB)、结合胆红素(CB)、非结合胆红素(UCB)、总胆汁酸(TBA)的含量,并对各组各项指标进行比较。结果:肝组织TNF-α、IL-6含量及MPO、XO、MDA的活性和血清TB、CB、UCB、TBA的含量随着I/R时间的延长而有逐渐升高和增强的趋势。与对照组、I组相比,I/R及I/R1、2、4h组各指标均明显升高和增强,差异有统计学意义(P<0.05);I/R1、2、4h组亦明显高于I/R组(P<0.05)。经相关性分析,TNF-α与IL-6、MPO、XO、MDA,MDA与TB、CB、UCB、TBA呈正相关。结论:肝I/R损伤可引起肝细胞XO活化,中性粒细胞浸润,释放的氧自由基及产生的TNF-α和IL-6可能参与了肝细胞损伤的发生机制,并导致高胆红素血症的发生。

Objective： To investigate the possible mechanisms of hyperbilirubinemia resulted from the liver ischemia/reperfusion（I/R）injury. Methods：Forty-eight healthy Wistar rats were randomly divided into six groups including the control, ischemia and four I/R （I/R, I/R1h, I/R2h and I/R4h） group. Each group contained eight rats. The contents in the liver tissue were respectively determined of tumor necrosis factor alpha （TNF-α）, interleukin-6 （IL-6）, myeloperoxidase （MPO）, xanthine oxidase （XO）, malondialdehyde （MDA）, serum total bilirubin （TB）, conjugated bilirubin （CB）, unconjugated bilirubin （UCB） and total bile acid （TBA） in each group. Comparisons were performed among the groups. Results： The contents of TNF-α and IL-6, the activity of MPO, XO increased gradually with the time extension of liver I/R. Compared with control and ischemia group, the contents in I/R, I/R1, I/R2 and I/R4h groups were significantly higher （P d0.05）. The I/Rlh, I/R2h and I/R4h group were higher than the I/R （P d0.05）. The positive correlation existed in TNF-α with IL-6, MPO, XO and MDA, MDA with TB, CB, UCB and TBA. Conclusion： Liver I/R injury could cause activation of XO in hepatic cell, infiltration of neutrophilic granulocyte, delivery of oxygen free radical and production of TNF-α and IL-6, which contributed to the mechanisms of hepatic cell injury and hyperbilirubinemia or hepaticogenic hyperbilirubinemia.