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缺血再灌注损伤后大鼠磷酸化p38丝裂原活化蛋白激酶的激活及其与肠干细胞定位的关系

Activation of phosphorylating-p38 mitogen-activated protein kinase and its relationship with localization of intestinal stem cells in rats after ischemia-reperfusion injury.

作者信息

Fu Xiao-Bing, Xing Feng, Yang Yin-Hui, Sun Tong-Zhu, Guo Bao-Chen

机构信息

Wound Healing and Cell Biology Laboratory, Institute of Burns, 304 Hospital, Trauma Center of Postgraduate Medical College, 51 Fu Cheng Road, Beijing 100037, China.

出版信息

World J Gastroenterol. 2003 Sep;9(9):2036-9. doi: 10.3748/wjg.v9.i9.2036.

DOI:10.3748/wjg.v9.i9.2036
PMID:12970901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4656669/
Abstract

AIM

To investigate the expression of phosphorylating p38 mitogen-activated protein kinase (MAPK) in rat small intestine after ischemia-reperfusion (I/R) insult and its relationship with the localization of intestinal stem cells.

METHODS

Forty-eight Wistar rats were divided randomly into three groups, namely intestinal ischemia-reperfusion group (R), intestinal ischemia group (I) and sham-operated control group (C). In group I, the animals were killed 45 minutes after superior mesenteric artery (SMA) occlusion, while in group R the rats sustained SMA occlusion for 45 minutes and reperfusion for 2, 6, 12 or 24 hours respectively. In sham-operated control group, SMA was separated, but without occlusion. The activity of plasma diamine oxidase (DAO) was determined. Intestinal tissue samples were also taken for histological analysis and immunohistochemical analysis of MAPK p38 detection and intestinal stem cell localization.

RESULTS

The changes in histological structure and plasma DAO levels indicated that the intestinal barrier was damaged after intestinal I/R injury. In group C and I, each crypt contained 5-6 p38 MAPK positive cells, which were mainly located in the lower region of the crypts. This was consistent with the distribution of intestinal stem cells. The presence of positive cells in crypts increased with the time of reperfusion and reached its peak at 12 hours after reperfusion (35.6 %).

CONCLUSION

After intestinal I/R injury, the expression of phosphorylating-p38 MAPK in small intestine increased with the duration of reperfusion, and its distribution coincided with that of intestinal stem cells and their daughter cells, indicating that phosphorylating-p38 might be a possible marker of intestinal stem cells.

摘要

目的

研究缺血再灌注(I/R)损伤后大鼠小肠中磷酸化p38丝裂原活化蛋白激酶(MAPK)的表达及其与肠干细胞定位的关系。

方法

48只Wistar大鼠随机分为三组,即肠缺血再灌注组(R)、肠缺血组(I)和假手术对照组(C)。I组动物在肠系膜上动脉(SMA)阻断45分钟后处死,而R组大鼠SMA阻断45分钟,分别再灌注2、6、12或24小时。假手术对照组分离SMA,但不阻断。测定血浆二胺氧化酶(DAO)活性。还取肠组织样本进行组织学分析以及MAPK p38检测和肠干细胞定位的免疫组织化学分析。

结果

组织结构和血浆DAO水平的变化表明肠I/R损伤后肠屏障受损。C组和I组中,每个隐窝含有5-6个p38 MAPK阳性细胞,主要位于隐窝下部。这与肠干细胞的分布一致。隐窝中阳性细胞的数量随再灌注时间增加,在再灌注12小时时达到峰值(35.6%)。

结论

肠I/R损伤后,小肠中磷酸化p38 MAPK的表达随再灌注时间延长而增加,其分布与肠干细胞及其子代细胞的分布一致,表明磷酸化p38可能是肠干细胞的一个潜在标志物。

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