Cherif-Sayadi Amani, Hadj Ayed-Tka Kaouther, Zaouali Mohamed Amine, Bejaoui Mohamed, Hadj-Abdallah Najet, Bouhlel Ahlem, Ben Abdennebi Hassen
a Research Unit of Biology and Molecular Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy , University of Monastir , Monastir , Tunisia.
b High Institute of Biotechnology of Monastir , University of Monastir , Monastir , Tunisia.
Libyan J Med. 2017 Dec;12(1):1308780. doi: 10.1080/19932820.2017.1308780.
Nitrite has been found to protect liver graft from cold preservation injury. However, the cell signaling pathway involved in this protection remains unclear. Here, we attempt to clarify if the NOS pathway by using the NOS inhibitor, L-NAME (L-N-Nitroarginine methyl ester).
Rat livers were conserved for 24 h at 4°C in (IGL-1) solution enriched or not with nitrite at 50 nM. In a third group, rats were pretreated with 50 mg/kg of L-NAME before their liver procurement and preservation in IGL-1 supplemented with nitrite (50 nM) and L-NAME (1 mM). After 24 h of cold storage, rat livers were ex-vivo perfused at 37°C during 2 h. Control livers were perfused without cold storage.
Nitrite effectively protected the rat liver grafts from the onset of cold I/R injury. L-NAME treatment did not abolish the beneficial effects of nitrite. Liver damage, protein oxidation and lipid peroxidation remained at low levels in both nitrite-treated groups when compared to IGL-1 group. Antioxidant enzyme activities and functional parameters were unchanged after NOS inhibition.
Despite NOS inhibition by L-NAME, nitrite can still provide hepatic protection during cold I/R preservation. This suggests that nitrite acts through a NOS-independent pathway.
已发现亚硝酸盐可保护肝移植免受冷保存损伤。然而，这种保护作用所涉及的细胞信号通路仍不清楚。在此，我们尝试通过使用一氧化氮合酶（NOS）抑制剂L-NAME（L-N-硝基精氨酸甲酯）来阐明是否涉及NOS通路。
将大鼠肝脏在4°C下于富含或不含50 nM亚硝酸盐的（IGL-1）溶液中保存24小时。在第三组中，大鼠在肝脏获取前用50 mg/kg的L-NAME预处理，并在补充有亚硝酸盐（50 nM）和L-NAME（1 mM）的IGL-1中保存。冷保存24小时后，大鼠肝脏在37°C下进行2小时的离体灌注。对照肝脏未经过冷保存直接进行灌注。
亚硝酸盐有效地保护大鼠肝移植免受冷缺血/再灌注（I/R）损伤的发生。L-NAME处理并未消除亚硝酸盐的有益作用。与IGL-1组相比，两个亚硝酸盐处理组的肝损伤、蛋白质氧化和脂质过氧化水平均保持在较低水平。一氧化氮合酶抑制后抗氧化酶活性和功能参数未发生变化。
尽管L-NAME抑制了一氧化氮合酶，但亚硝酸盐在冷I/R保存期间仍可提供肝脏保护。这表明亚硝酸盐通过一条不依赖一氧化氮合酶的途径发挥作用。
