Ischemic preconditioning enhances regenerative capacity of hepatocytes in long-term ischemically damaged rat livers
Ischemic preconditioning enhances regenerative capacity of hepatocytes in long-term ischemically damaged rat livers
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DOI：
10.1111/j.1440-1746.2006.04711.x
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发表时间：
2007-11-01
影响因子：
4.1
通讯作者：
Gotoh, Mitsukazu
中科院分区：
文献类型：
--
作者：
Yamada, Fumihiko;Saito, Takuro;Gotoh, Mitsukazu
背景与目的：缺血预处理（IPC）可保护组织免受缺血再灌注（I/R）损伤。本研究的目的是研究IPC对长期I/R损伤后肝细胞的保护和再生的影响。方法：采用大鼠节段性（70%）肝缺血模型，观察在肝缺血40,60,90,120 min前10 min IPC的影响。通过比较肝脏的细胞溶解标记物和坏死区域，以及使用增殖细胞核抗原标记指数（PCNA-LI）和缺血肝叶的重量来评估肝细胞的再生能力，来评估其效果。采用免疫组织化学方法研究蛋白激酶B/Akt （Akt）和caspase-9对存活和抗凋亡信号激活的影响。结果：在肝局灶性坏死的40min I/R模型中，IPC通过降低局灶性坏死的面积、pna - li水平以及对Akt和caspase-9的免疫反应，对I/R损伤具有明显的保护作用。相比之下，IPC在90和120分钟的缺血性肝坏死模型中没有预防缺血性损伤。然而，与对照组相比，IPC增强了剩余肝细胞的再生能力，其pna - li水平、akt阳性细胞数量和术后肝叶平均重量均高于对照组。结论：在肝局灶性坏死模型中，IPC可保护肝细胞免受I/R损伤。此外，在大面积坏死模型中，IPC通过增强存活信号维持剩余肝细胞的再生能力。
Background and Aims: Ischemic preconditioning (IPC) protects tissues against ischemia and reperfusion (I/R) injury. The aim of this study was to examine the impact of IPC on protection and regeneration of hepatocytes after prolonged I/R injury.Methods: A rat model of segmental (70%) hepatic ischemia was used to determine the effect of 10-min IPC preceding 40, 60, 90, or 120 min of liver ischemia. The effect was assessed by comparing cytolysis markers and necrotic areas of the liver, as well as the regenerative capacity of hepatocytes using the proliferating cell nuclear antigen labeling index (PCNA-LI) and weight of the ischemic liver lobe. Protein kinase B/Akt (Akt) and caspase-9 were investigated immunohistochemically to determine the effect of IPC on activation of survival and anti-apoptotic signals.Results: In the model of 40 min I/R, which resulted in focal necrosis of the liver, IPC significantly protected against I/R injury by reducing the area of focal necrosis, level of PCNA-LI and immunoreactivities to Akt and caspase-9. In contrast, IPC did not prevent ischemic damage in the 90- and 120-min ischemic model with massive liver necrosis. However, IPC enhanced the regenerative capacity of the remaining hepatocytes with higher levels of PCNA-LI, number of Akt-positive cells and mean weight of the liver lobe postoperatively than in the controls.Conclusions: In a model of focal necrosis of the liver, IPC protected hepatocytes against I/R injury. In addition, in a model of massive necrosis, IPC maintained the regenerative capacity of the remaining hepatocytes by enhancing the survival signals.