冷保存再灌注损伤对大鼠移植肝术后早期胆盐分泌的影响

目的 探讨大鼠移植肝脏经历冷保存再灌注损伤（CPRI）后胆盐谱的变化规律。方法 建立专门用于胆汁胆盐检测的柱前衍生反相高效液相色谱法（RP—HPLC）。大鼠被随机分为对照组（A组,n=6）、供肝冷保存1h组（B组,n=6）和供肝冷保存12h组（C组,n=6）。对各组大鼠术后14d的胆汁标本进行RP—HPLC分析。结果 共检出11种胆盐。CPRI可以显著影响大鼠移植肝胆盐的组成,主要表现为疏水性的牛磺胆酸和牛磺脱氧胆酸比重的持续增加以及亲水性的牛磺猪脱氧胆酸和牛磺熊脱氧胆酸比重的一过性升高。术后1～4d,胆盐疏水指数（HI）无显著变化;从术后5d开始,胆盐HI显著上升,术后7～10d达到高峰。且供肝冷保存时间越长,HI升高越显著。结论 经历CPRI后,移植肝胆汁疏水性胆盐比重的上升可能是导致胆汁细胞毒性增加的主要原因之一。

Effect of cold preservation and reperfusion injury on early-stage bile salt secretion after liver transplantation in rat model

OBJECTIVE: To explore the effect of cold preservation and reperfusion injury (CPRI) on the bile salt spectrum in rat orthotopic liver transplantation (OLT) model. METHODS: A special analysis method was established to investigate the bile salts in rat by reverse phase high performance liquid chromatography (RP-HPLC). Rats were randomly divided into 3 groups: group A (control group, n = 6), group B (group with 1 h graft preversation pre-OLT, n = 6) and group C (group with 12 h graft preversation pre-OLT, n = 6). The bile samples of 0 - 14 post-transplantation days were analyzed by RP-HPLC. RESULTS: Eleven kinds of bile salts were detected in rat bile. It showed that CPRI could influence the concentration of bile salts significantly in rat model after OLT, the concentration of hydrophobic bile salts (TCA and TCDCA) increased significantly in group B and C. However, the concentration of hydrophilic bile salts (TUDCA and THDCA) just increased in a short-time. The hydrophobicity index (HI) wasn't significantly changed during the first 4 post-transplant days. Thus the HI of bile salts elevated gradually from the 5th day and reached the peak at the 10th day after OLT. CONCLUSION: The increase of the proportion of hydrophobic bile salts may be one of the major factors leading to the increase of bile toxicity after OLT.