Tabka Donia, Bejaoui Mohamed, Javellaud James, Roselló-Catafau Joan, Achard Jean-Michel, Abdennebi Hassen Ben
Donia Tabka, Hassen Ben Abdennebi, Unité de recherche "Biologie et anthropologie moléculaire appliquées au développement et à la santé" (UR12ES11), University of Monastir, Faculty of Pharmacy, Monastir 5000, Tunisia.
World J Gastroenterol. 2015 Apr 14;21(14):4159-68. doi: 10.3748/wjg.v21.i14.4159.
To compare Institut Georges Lopez (IGL-1) and Celsior preservation solutions for hepatic endothelium relaxation and liver cold ischemia reperfusion injury (IRI).
Two experimental models were used. In the first one, acetylcholine-induced endothelium-dependent relaxation (EDR) was measured in isolated ring preparations of rat hepatic arteries preserved or not in IGL-1 or Celsior solutions (24 h at 4 °C). To determine nitric oxide (NO) and cyclooxygenase EDR, hepatic arteries were incubated with L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of endothelium nitric oxide synthase (eNOS), or with L-NAME plus indomethacin, an inhibitor of cyclooxygenase. In the second experiment, rat livers were cold-stored in IGL-1 or Celsior solutions for 24 h at 4 °C and then perfused "ex vivo" for 2 h at 37 °C. Liver injury was assessed by transaminase measurements, liver function by bile production and bromosulfophthalein clearance, oxidative stress by malondialdehyde levels and catalase activity and alterations in cell signaling pathways by pAkt, pAMPK, eNOS and MAPKs proteins level.
After cold storage for 24 h with either Celsior or IGL-1, EDR was only slightly altered. In freshly isolated arteries, EDR was exclusively mediated by NO. However, cold-stored arteries showed NO- and COX-dependent relaxation. The decrease in NO-dependent relaxation after cold storage was significantly more marked with Celsior. The second study indicated that IGL-1 solution obtained better liver preservation and protection against IRI than Celsior. Liver injury was reduced, function was improved and there was less oxidative stress. IGL-1 solution activated Akt and AMPK, which was concomitant with increased eNOS expression and nitrite/nitrate levels. Furthermore, MAPKs kinases were regulated in livers preserved with IGL-1 solution since reductions in p-p38, p-ERK and p-JNK protein levels were observed.
IGL-1 solution preserved NO-dependent relaxation better than Celsior storage solution and enhanced liver graft preservation.
比较乔治·洛佩斯研究所（IGL-1）保存液和赛而斯欧（Celsior）保存液对肝内皮舒张及肝脏冷缺血再灌注损伤（IRI）的影响。
采用两种实验模型。第一种，在IGL-1或赛而斯欧保存液中保存或未保存的大鼠肝动脉离体环标本（4℃下保存24小时）中，测量乙酰胆碱诱导的内皮依赖性舒张（EDR）。为确定一氧化氮（NO）和环氧合酶介导的EDR，肝动脉与内皮型一氧化氮合酶（eNOS）抑制剂L-NG-硝基精氨酸甲酯（L-NAME）或与L-NAME加环氧合酶抑制剂吲哚美辛共同孵育。在第二个实验中，将大鼠肝脏在4℃下于IGL-1或赛而斯欧保存液中冷藏24小时，然后在37℃下“离体”灌注2小时。通过转氨酶测量评估肝损伤，通过胆汁生成和溴磺酞钠清除评估肝功能，通过丙二醛水平和过氧化氢酶活性评估氧化应激，并通过pAkt、pAMPK、eNOS和丝裂原活化蛋白激酶（MAPKs）蛋白水平评估细胞信号通路的改变。
用赛而斯欧或IGL-1冷藏24小时后，EDR仅略有改变。在新鲜分离的动脉中，EDR仅由NO介导。然而冷藏后的动脉显示出NO和COX依赖性舒张。冷藏后赛而斯欧保存液导致的NO依赖性舒张降低更为明显。第二项研究表明，与赛而斯欧相比，IGL-1保存液能更好地保存肝脏并保护其免受IRI损伤。肝损伤减轻，肝功能改善，氧化应激减少。IGL-1保存液激活了Akt和AMPK，这与eNOS表达增加和亚硝酸盐/硝酸盐水平升高相关。此外，在用IGL-1保存液保存的肝脏中，MAPKs激酶受到调节，因为观察到p-p38、p-ERK和p-JNK蛋白水平降低。
IGL-1保存液比赛而斯欧保存液能更好地保存NO依赖性舒张，并增强肝脏移植物的保存效果。
