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尼可地尔对犬小肠缺血再灌注损伤的影响。

The effect of nicorandil on small intestinal ischemia-reperfusion injury in a canine model.

机构信息

Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

出版信息

Dig Dis Sci. 2011 Aug;56(8):2276-82. doi: 10.1007/s10620-011-1623-0. Epub 2011 Mar 1.

Abstract

BACKGROUND

It has been shown that nicorandil, which has both ATP-sensitive K+ (KATP) channel opener-like and nitrate-like properties, has an organ-protective effect in ischemia-reperfusion injury in several experimental animal models.

AIMS

We evaluate the effectiveness of nicorandil on warm ischemia-reperfusion injury of the small intestine in a canine model.

METHODS

Eighteen beagle dogs were divided into three groups: the control group (n=6); the nicorandil group (n=6), to which nicorandil was injected intravenously before the ischemia; and the glibenclamide group (n=6), to which glibenclamide, which closes the KATP channel and does not suppress the nitrate effect of nicorandil, was orally administered, and then nicorandil was injected in the same manner as in the nicorandil group. Both the superior mesenteric artery and vein were clamped for 2 h. Superior mesenteric artery blood flow, small intestinal mucosal tissue blood flow, intramucosal pH, and histopathological analyses were compared among the three groups.

RESULTS

Superior mesenteric artery blood flow, mucosal tissue blood flow and pHi after reperfusion were significantly maintained in the nicorandil in comparison with the control and the glibenclamide groups. The histopathological findings showed less severe mucosal damage after reperfusion in the nicorandil group compared with the other two groups. Between the control group and the glibenclamide group, no significant differences were observed in all those parameters.

CONCLUSION

This study suggests that nicorandil has a protective effect on small intestinal IR injury, and activation of KATP channels plays an important role in inhibiting small intestinal IR injury.

摘要

背景

已有研究表明,具有三磷酸腺苷敏感性钾通道(KATP)开放剂样和硝酸盐样特性的尼可地尔在几种实验动物模型的缺血再灌注损伤中具有器官保护作用。

目的

我们评估尼可地尔对犬小型肠缺血再灌注损伤的有效性。

方法

18 只比格犬分为三组:对照组(n=6);尼可地尔组(n=6),在缺血前静脉注射尼可地尔;以及格列本脲组(n=6),给予格列本脲(一种关闭 KATP 通道但不抑制尼可地尔硝酸盐作用的药物)口服,然后以与尼可地尔组相同的方式注射尼可地尔。夹闭肠系膜上动、静脉 2 小时。比较三组间肠系膜上动脉血流量、黏膜组织血流、黏膜内 pH 值和组织病理学分析。

结果

与对照组和格列本脲组相比,尼可地尔组再灌注后肠系膜上动脉血流量、黏膜组织血流和 pHi 明显维持。尼可地尔组再灌注后的黏膜损伤较其他两组明显减轻。在对照组和格列本脲组之间,所有这些参数均无显著差异。

结论

本研究表明,尼可地尔对小肠缺血再灌注损伤具有保护作用,KATP 通道的激活在抑制小肠缺血再灌注损伤中发挥重要作用。

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