Adenosine A1 receptor agonism protection mechanism in intestinal ischemia/reperfusion injury via activation of PI3K/Akt signaling

腺苷A1受体激动剂通过激活PI3K/Akt信号在肠缺血/再灌注损伤中的保护机制

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作者:Qian Xu, Zun Mao, Yi Yun

Abstract

Intestinal ischemia/reperfusion (I/R) injury is a common clinical problem with a high mortality rate, resulting from loss of blood flow to an intestinal segment. Adenosine serves a protective role in intestinal I/R injury; however, its potential mechanism is not completely understood. The present study aimed to investigate the protective effects of adenosine A1 receptor (A1R) agonists CPA and LUF6941 and whether their mechanisms are associated with the PI3K/Akt signaling pathway. To simulate intestinal I/R injury, a cell oxygen-glucose deprivation/reoxygenation (OGD/R) model was established and the human colon cancer cell line (Caco-2) was incubated with A1R agonists before OGD/R treatment. The viability of Caco-2 cells was detected by PI and Cell Counting Kit-8 assay, apoptosis was detected using flow cytometry and western blotting was used to analyze protein expression levels of PI3K, Akt and p53 in Caco-2 cells. A1R agonist pretreatment protected Caco-2 cells against OGD/R-induced cell damage and activated PI3K/Akt signaling. Additionally, apoptosis was inhibited by downregulating phosphorylation of p53 protein, as evidenced by increased cell viability. These findings suggested that A1R agonists decreased OGD/R damage in Caco-2 cells, which may be due to their anti-apoptotic effects and activation of the PI3K/Akt/p53 signal pathway.

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