Silva Michael A, Mirza Darius F, Murphy Nick, Richards Douglas A, Reynolds Gary M, Wigmore Stephen J, Neil Desley A H
The Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham B15 2TH, United Kingdom.
Transplantation. 2008 Mar 15;85(5):718-25. doi: 10.1097/TP.0b013e3181663366.
Changes in glucose metabolism in the liver during transplantation have been recently described using microdialysis. Here, these findings are correlated with histopathologic, immunohistochemical, and ultrastructural changes in liver.
Microdialysis catheters were inserted into 15 human livers, which were perfused with isotonic solution, and samples of perfusate were analyzed before harvest, after storage, and after reperfusion. At each stage Menghini needle biopsy samples were taken and each studied using light and electron microscopy.
Six livers showed serum biochemical evidence of initial poor function. These livers had significantly more staining for complement fragment 4d (C4d) of both lobular and periportal hepatocytes. C4d-positive hepatocytes were also found in the liver during cold storage (3 of 15). These periportal hepatocytes also showed evidence of necrosis and were found to have intracellular neutrophils. Hepatocyte rounding in zone III, necrosis, and C4d staining in recipient were also significantly correlated with the degree of lactic acidosis during this phase. Intrahepatic lactic acidosis at all time points was significantly associated with sinusoidal endothelial cell injury after reperfusion. There were no correlations between glucose, pyruvate, and glycerol levels and histopathologic changes in the liver.
In the patients studied, the degree of C4d staining correlated with initial poor function and was associated with intrahepatic lactic acidosis in the donor during cold storage and after reperfusion. Complement activity in the liver during cold storage may be after in situ activation. Intrahepatic lactic acidosis is associated with sinusoidal endothelial cell and hepatocyte injury. The role of intrahepatic neutrophils is uncertain and could possibly be in response to cell necrosis.
最近已使用微透析描述了移植过程中肝脏葡萄糖代谢的变化。在此，这些发现与肝脏的组织病理学、免疫组织化学和超微结构变化相关。
将微透析导管插入15个灌注等渗溶液的人体肝脏中，在收获前、储存后和再灌注后分析灌注液样本。在每个阶段采集Menghini针活检样本，并分别使用光学显微镜和电子显微镜进行研究。
6个肝脏显示出初始功能不佳的血清生化证据。这些肝脏的小叶和门周肝细胞的补体片段4d（C4d）染色明显更多。在冷保存期间（15个中有3个）肝脏中也发现了C4d阳性肝细胞。这些门周肝细胞也显示出坏死迹象，并发现有细胞内中性粒细胞。受体中III区肝细胞变圆、坏死和C4d染色也与该阶段乳酸酸中毒的程度显著相关。再灌注后所有时间点的肝内乳酸酸中毒均与窦状内皮细胞损伤显著相关。葡萄糖、丙酮酸和甘油水平与肝脏组织病理学变化之间无相关性。
在所研究的患者中，C4d染色程度与初始功能不佳相关，并与供体在冷保存期间和再灌注后的肝内乳酸酸中毒有关。冷保存期间肝脏中的补体活性可能是原位激活后的结果。肝内乳酸酸中毒与窦状内皮细胞和肝细胞损伤有关。肝内中性粒细胞的作用尚不确定，可能是对细胞坏死的反应。
