Role of Endothelial Nitric Oxide Synthase in Remote Ischemic Preconditioning of the Mouse Liver
Role of Endothelial Nitric Oxide Synthase in Remote Ischemic Preconditioning of the Mouse Liver
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DOI：
10.1002/lt.22272
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发表时间：
2011-05-01
影响因子：
4.6
通讯作者：
Davidson, Brian
中科院分区：
文献类型：
--
作者：
Abu-Amara, Mahmoud;Yang, Shi Yu;Davidson, Brian
后肢远程缺血预处理 (RIPC) 可减少野生型小鼠的肝脏缺血/再灌注 (IR) 损伤。 RIPC 的潜在机制目前尚不清楚。在本研究中，我们研究了内皮型一氧化氮合酶 (eNOS) 在介导 RIPC 保护作用中的作用。内皮一氧化氮合酶敲除（eNOS（-/-））小鼠分为4组：（1）假手术组，（2）RIPC组（6个周期，4分钟后肢缺血和4分钟后肢再灌注），（3）IR组[40分钟脑叶（70％）肝缺血和2小时再灌注]，（4） RIPC+IR 组（RIPC 后进行 IR 组程序）。评估了血浆肝脏转氨酶、肝脏组织病理学损伤评分、透射电子显微镜研究和肝脏微循环血流量（MBF）。对野生型小鼠的肝脏和后肢肌肉中的 eNOS 蛋白表达进行了分析。 Hindlimb RIPC 不能保护 eNOS(-/-) 小鼠随后的肝脏 IR 损伤；与 IR 组相比，RIPC+IR 组的血浆转氨酶水平、组织病理学评分或 IR 损伤的超微结构特征没有降低，证明了这一点。与 IR 组相比，RIPC+IR 组在肝脏再灌注期间肝脏 MBF 没有恢复。所有野生型组中的 eNOS 蛋白表达相似。总之，eNOS 对于后肢 RIPC 对肝脏 IR 损伤的保护作用至关重要。 eNOS 通过保存肝脏 MBF 发挥其保护作用。再灌注 2 小时，eNOS 保护可能是由于 eNOS 激活增加而不是表达增加。肝脏移植 17:610-619, 2011。(C) 2011 AASLD。
Hindlimb remote ischemic preconditioning (RIPC) reduces liver ischemia/reperfusion (IR) injury in wild-type mice. The underlying mechanisms of RIPC are currently unknown. In this study, we investigated the role of endothelial nitric oxide synthase (eNOS) in mediating the protective effects of RIPC. Endothelial nitric oxide synthase knockout (eNOS(-/-)) mice were divided into 4 groups: (1) a sham surgery group, (2) an RIPC group (6 cycles of 4 minutes of hindlimb ischemia and 4 minutes of hindlimb reperfusion), (3) an IR group [40 minutes of lobar (70%) hepatic ischemia and 2 hours of reperfusion], and (4) an RIPC+IR group (RIPC followed by the IR group procedures). Plasma liver aminotransferases, hepatic histopathological injury scores, transmission electron microscopy studies, and hepatic microcirculatory blood flow (MBF) were assessed. eNOS protein expression was analyzed in the livers and hindlimb muscles of wild-type mice. Hindlimb RIPC did not protect against subsequent liver IR injury in eNOS(-/-) mice; this was demonstrated by the lack of reduction in the plasma aminotransferase levels, histopathological scores, or ultrastructural features of IR injury in the RIPC+IR group versus the IR group. Hepatic MBF did not recover during liver reperfusion in the RIPC+IR group versus the IR group. eNOS protein expression was similar among all wild-type groups. In conclusion, eNOS is essential for the protective effects of hindlimb RIPC on liver IR injury. eNOS exerts its protective effects through the preservation of hepatic MBF. At 2 hours of reperfusion, eNOS protection is likely due to the increased activation of eNOS rather than increased expression. Liver Transpl 17:610-619, 2011. (C) 2011 AASLD.