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Ischemic post-conditioning alleviates I/R lung injury by activating PI3K/AKT pathway in rats

YAN Wang-Xin¹, CHENG Yuan², HUANG Man², XU Jun-Peng², LUO Zhen-Zhen², WANG Shu-Yuan³, DAI Yong-Yue², YOU Li-Yi⁴, WANG Wan-Tie^2,*

¹Department of Colorectal and Anal Surgery, Wenzhou People's Hospital, Wenzhou 325400, China；²Institute of Ischemia/Reperfusion Injury, Wenzhou Medical University, Wenzhou 325035, China；³Department of Respiratory Medicine, Wenzhou People's Hospital, Wenzhou 325400, China；⁴Department of Ultrasound, Wenzhou People's Hospital, Wenzhou 325400, China

Abstract

The present study aimed to investigate whether ischemic post-conditioning (I-post-C) could reduce lung ischemia/reperfusion injury (LIRI) by activating PI3K/AKT pathway in rats. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into four groups: control group, ischemia/reperfusion (I/R) group, I-post-C group, and I-post-C+PI3K inhibitor (I-post-C+LY294002) group. The left pulmonary hilum of rats in the I/R group was clamped for 30 min with a miniature arterial clip and then released, followed by reperfusion for 1 h; the left pulmonary hilum of rats in the I-post-C group was blocked for 30 min, followed by reperfusion for 30 s, and this process was repeated three times before reperfusion for 1 h; rats in the I-post-C+LY294002 group were intraperitoneally injected with LY294002 (10 mg/kg) once a day for 3 d before surgery, and the subsequent treatment was the same as that of the I-post-C group. Lung tissue injury was assessed using HE staining and calculation of total lung water content (TLW), index of quantitative assessment (IQA), and lung wet-to-dry weight ratio (W/D). TUNEL assay was used to detect the level of apoptosis in lung tissue. Western blot was used to detect the activation level of Caspase 3 (cleaved Caspase 3/pro-Caspase 3 ratio) and the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and glycogen synthase kinase 3β (GSK-3β) in lung tissue. Mitochondrial membrane potential was measured by JC-1 staining. The results showed that compared with the control group, the I/R group exhibited significant lung tissue damage, a significant decrease in mitochondrial membrane potential, significantly elevated cleaved Caspase 3/pro-Caspase 3 ratio and cell apoptosis level, as well as decreased phosphorylation levels of PI3K/AKT/GSK-3β. I-post-C significantly reversed the aforementioned changes in lung tissue of the I/R group and exerted a protective effect on lung tissue. The PI3K inhibitor LY294002 partially eliminated this lung protective effect of I-post-C. These results suggest that I-post-C activates the PI3K/AKT pathway to inactivate GSK-3β, inhibits mitochondrial membrane potential decline, antagonizes lung tissue cell apoptosis, and thereby alleviates LIRI.

Key words: Rats; ischemic post-conditioning; ischemia/reperfusion injury; apoptosis; PI3K/AKT pathway

Received: 　　Accepted:

Corresponding author: 王万铁　　E-mail:

DOI: 10.13294/j.aps.2026.0050

Citing This Article：

YAN Wang-Xin, CHENG Yuan, HUANG Man, XU Jun-Peng, LUO Zhen-Zhen, WANG Shu-Yuan, DAI Yong-Yue, YOU Li-Yi, WANG Wan-Tie. Ischemic post-conditioning alleviates I/R lung injury by activating PI3K/AKT pathway in rats. Acta Physiol Sin 2026; 78 (3): 705-712 (in Chinese with English abstract).