Nickkholgh Arash, Li Zhanqing, Yi Xue, Mohr Elvira, Liang Rui, Mikalauskas Saulius, Gross Marie-Luise, Zorn Markus, Benzing Steffen, Schneider Heinz, Büchler Markus W, Schemmer Peter
Department of General and Transplant Surgery, Ruprecht-Karls University, 69120 Heidelberg, Germany.
HPB Surg. 2012;2012:783479. doi: 10.1155/2012/783479. Epub 2012 Jun 25.
Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.
背景。已经提出了几种药理学方法来改善肝脏缺血/再灌注损伤（IRI）。本研究旨在评估一种含有谷氨酰胺、抗氧化剂和绿茶提取物的预处理口服营养补充剂（pONS）对猪肝脏热缺血IRI的影响。方法。将pONS（每份70克，德国费森尤斯卡比公司生产）溶解于250毫升自来水中，在肝脏热缺血前24小时、12小时和2小时给予猪。再灌注后3小时给予第四剂。对照组给予相同量的纤维素和相同体积的水。在第三剂pONS给药2小时后，夹闭门静脉和肝动脉40分钟。再灌注后0.5小时、3小时、6小时和8小时，测量心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）、门静脉血流（PVF）、肝动脉血流（HAF）、胆汁流量和转氨酶。再灌注8小时后取肝脏组织进行组织学和免疫组织化学检查。结果。两组之间的HR、MAP、CVP、HAF和PVF相当。pONS显著增加再灌注8小时后的胆汁流量。pONS给药后ALT和AST显著降低。组织学显示对照组坏死和中性粒细胞浸润明显更严重。pONS显著降低TNF-α、MPO和裂解的caspase-3免疫组化表达指数（P < 0.001）。结论。在组织损伤前后给予pONS可通过降低氧化应激、脂质过氧化、细胞凋亡和坏死等机制保护肝脏免受热缺血IRI的损伤。
