Hepatology Unit, Department of Internal Medicine, University of Tor Vergata, Via Montpellier 1, Rome, Italy.
Transpl Int. 2012 Dec;25(12):1282-8. doi: 10.1111/j.1432-2277.2012.01555.x. Epub 2012 Sep 13.
Leptin is an adipocytokine that reduces ischemic damage in several organs including brain and heart. STAT3 activation is a key step for the attainment of leptin effects in various tissues. We evaluated the possible effect of leptin on liver viability and STAT3 activation, in a rat model of ischemia-reperfusion injury. Rat livers, flushed and stored with Belzer solution (4° C for 24 h), were warmly reperfused (3.5 ml/min/g liver for 1 h at 37° C with O(2) ) with Krebs-Ringer bicarbonate. Treatment group underwent an identical protocol with the adjunct of Leptin (10 ng/ml). Liver effluent was harvested to assess LDH and AST output. Liver tissue was used for pSTAT3 expression (western blot and immunostaining), optical microscopy, TUNEL, and Cell Death Detection assays. The pSTAT3 expression was enhanced by administration of leptin. In parallel, LDH and AST output were reduced (P = 0.04 and P = 0.02 for LDH and AST, respectively). Optical microscopy, TUNEL, and Cell Death Detection assay results demonstrated increased viability in livers treated with leptin in comparison with others (Optical microscopy P = 0.02; TUNEL P = 0.01; Cell death Detection assay P = 0.003). In conclusion, cold storage and reperfusion with leptin reduce liver ischemia-reperfusion injury. This effect is associated with an increased expression of pSTAT-3.
瘦素是一种脂肪细胞因子，可减少包括大脑和心脏在内的多种器官的缺血性损伤。STAT3 激活是瘦素在各种组织中发挥作用的关键步骤。我们评估了瘦素对肝脏活力和 STAT3 激活的可能影响，这是在大鼠缺血再灌注损伤模型中进行的。用 Belzer 溶液（4°C 保存 24 小时）冲洗和保存大鼠肝脏，在 37°C 下用 O(2)以 3.5ml/min/g 肝脏的速度进行温暖再灌注（1 小时）。治疗组进行了相同的方案，同时给予瘦素（10ng/ml）。采集肝流出物以评估 LDH 和 AST 产量。使用 Western blot 和免疫染色法检测肝组织中 pSTAT3 的表达，进行光学显微镜检查、TUNEL 和细胞死亡检测分析。瘦素给药可增强 pSTAT3 的表达。同时，LDH 和 AST 的产量降低（LDH 和 AST 的 P 值分别为 0.04 和 0.02）。与其他组相比，用瘦素处理的肝脏在光学显微镜（P=0.02）、TUNEL（P=0.01）和细胞死亡检测分析（P=0.003）中显示出更高的活力。总之，冷保存和再灌注加用瘦素可减轻肝脏缺血再灌注损伤。这种作用与 pSTAT3 表达的增加有关。
