转录因子在小肠缺血再灌注损伤及缺血预处理诱导的耐受性中的作用。

Role of transcription factors in small intestinal ischemia-reperfusion injury and tolerance induced by ischemic preconditioning.

作者信息

Takeshita M, Tani T, Harada S, Hayashi H, Itoh H, Tajima H, Ohnishi I, Takamura H, Fushida S, Kayahara M

机构信息

Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.

出版信息

Transplant Proc. 2010 Nov;42(9):3406-13. doi: 10.1016/j.transproceed.2010.06.038.

DOI:10.1016/j.transproceed.2010.06.038

PMID:21094787

Abstract

BACKGROUND

Small intestinal ischemia-reperfusion (I/R) injury, a clinically important condition, induces severe organ damage. Ischemic preconditioning (IPC) produces tolerance to long-term I/R by inducing a short-term I/R. Herein, we have examined the reduction in the extent of injury by IPC.

METHODS

Small intestinal I/R injury was induced in rats by clamping the superior mesenteric artery (SMA) for 30 minutes followed by reperfusion for various 30 minutes. The IPC + I/R group underwent a short-term I/R (IPC) prior to long-term I/R. Nuclear factor-κB (NF-κB) activity was analyzed by an electrophoretic mobility shift assay and cytokine mRNA levels, by reverse transcription-polymerase chain reaction. Apoptosis-related genes were analyzed by Western blotting and immunohistochemistry, and apoptotic cells, by TUNEL staining.

RESULTS

The animals were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. NF-κB activity increased in the I/R group and decreased in the IPC + I/R group. The IPC + I/R group showed decreased cytokine in mRNA levels. Expression of the proapoptotic gene caspase-3 was increased in the I/R and decreased in the IPC + I/R group. Expression of the antiapoptotic gene Bcl-xL was increased in the IPC + I/R group. The number of apoptotic cells was increased in the I/R and decreased in the IPC + I/R group.

CONCLUSION

Small intestinal I/R injury was reduced by IPC produced by clamping the SMA; thus, IPC may have potential clinical applications in the future.

摘要

背景

小肠缺血再灌注（I/R）损伤是一种具有临床重要性的病症，可导致严重的器官损害。缺血预处理（IPC）通过诱导短期I/R产生对长期I/R的耐受性。在此，我们研究了IPC对损伤程度的减轻作用。

方法

通过夹闭肠系膜上动脉（SMA）30分钟，然后再灌注30分钟，诱导大鼠小肠I/R损伤。IPC + I/R组在长期I/R之前先进行短期I/R（IPC）。通过电泳迁移率变动分析检测核因子-κB（NF-κB）活性，通过逆转录-聚合酶链反应检测细胞因子mRNA水平。通过蛋白质印迹和免疫组织化学分析凋亡相关基因，通过TUNEL染色分析凋亡细胞。

结果

动物经历30分钟的缺血，随后30分钟的再灌注。NF-κB活性在I/R组中增加，在IPC + I/R组中降低。IPC + I/R组细胞因子mRNA水平降低。促凋亡基因caspase-3的表达在I/R组中增加，在IPC + I/R组中降低。抗凋亡基因Bcl-xL的表达在IPC + I/R组中增加。凋亡细胞数量在I/R组中增加，在IPC + I/R组中减少。