Chung Wen Yuan, Gravante Gianpiero, Al-Leswas Dhya, Alzaraa Ahmed, Sorge Roberto, Ong Seok Ling, Pollard Cristina, Lloyd David M, Metcalfe Matthew S, Dennison Ashley R
Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University of Leicester, Gwendolen Road, Leicester LE5 4PW, UK.
J Artif Organs. 2012 Sep;15(3):290-4. doi: 10.1007/s10047-012-0641-9. Epub 2012 Apr 4.
The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.
在体外肝脏灌注模型中添加肾脏可能有助于维持重要生化参数(如pH值变化、尿素和肌酐或葡萄糖水平)的循环稳态平衡,但也可能增加所产生的炎症反应。在本研究中,我们比较了肝肾联合灌注回路和单纯肝脏灌注回路中各种细胞因子的产生情况。从雌性猪身上获取7个肝脏,并进行6小时的灌注。在另外5个实验中,还获取了一个肾脏并与肝脏并联连接。在灌注前以及灌注后第1、2、4和6小时采集血液样本,检测白细胞介素(IL)-1、-2、-4、-6、-8、-10和-12、干扰素(IFN)-γ以及肿瘤坏死因子(TNF)-α。在肝肾联合灌注回路中,仅IL-6和IL-8有显著增加,但与单纯肝脏灌注回路中记录的水平相比,差异无统计学意义。所有其他细胞因子与基线水平相比无变化。在灌注回路中添加肾脏不会比单纯肝脏灌注引发更强烈的炎症反应,因此鉴于需要严格稳态条件的更精细实验,进一步证实了实验设置的安全性。