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Updated: Mar 1, 2026
Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction
Published on: May 28, 2019
Myocardial ischemic post-conditioning protects the lung against myocardial ischemia/reperfusion-induced damage by
Wenwei Gao1, Bo Zhao2, Lian Liu3
1Doctor of Medicine, Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China. Conception and design of the study, acquisition and interpretation of data, manuscript writing.
Purpose::
To investigate whether modulating GSK-3β could attenuate myocardial ischemia reperfusion injury (MIRI) induced acute lung injury (ALI) and analyze the underlying mechanism.
Methods::
Male SD rats were subjected to MIRI with or without myocardial ischemic post-conditioning in the presence or absence of GSK-3β inhibitor. GSK-3β inhibitor was injected peritoneally 10min before MIRI. Lung W/D weight ratio, MPO, PMNs, histopathological changes, TUNEL, Bax, Bcl-2, IL-6, IL-8, IL-10, GSK-3β, and caspase-3 were evaluated in the lung tissues of all rats.
Results::
After MIRI, lung injury was significantly increased manifested as significant morphological changes and increased leukocytes in the interstitial capillaries, Lung W/D ratio, MPO, and PMN in BALF, which was associated with enhanced inflammation evidenced by increased expressions of IL-6, IL-8 and reduced expression of IL-10. MIRI significantly increased cell apoptosis in the lung as increased levels of apoptotosis, Bax, cleaved caspase-3, and reduced expression of Bcl-2 was observed, which was concomitant with reduced p-GSK-3β. All these changes were reversed/prevented by ischemic post-conditioning, while these beneficial effects of ischemic post-conditioning were abolished by GSK-3β inhibition.
Conclusion::
Myocardial ischemia reperfusion injury induces acute lung injury by induction of inflammation and cell apoptosis. Ischemic post-conditioning protects the lung from ALI following MIRI by increasing p-GSK-3β.
Insights
Myocardial ischemia reperfusion injury causes acute lung injury via inflammation and apoptosis. Ischemic post-conditioning protects the lung by increasing GSK-3β activity, but this effect is blocked by GSK-3β inhibition.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Cellular Biology
Background:
- Myocardial ischemia reperfusion injury (MIRI) can lead to acute lung injury (ALI).
- The precise mechanisms linking MIRI to ALI, particularly involving inflammation and apoptosis, require further elucidation.
- Glycogen synthase kinase 3 beta (GSK-3β) plays a role in cellular injury pathways.
Purpose of the Study:
- To investigate if modulating GSK-3β can attenuate MIRI-induced ALI.
- To analyze the underlying molecular mechanisms of this interaction.
- To determine the role of GSK-3β in the protective effects of ischemic post-conditioning.
Main Methods:
- Male Sprague-Dawley rats underwent MIRI with or without ischemic post-conditioning and GSK-3β inhibitor administration.
- Evaluated lung injury markers including wet/dry weight ratio, myeloperoxidase (MPO), and polymorphonuclear neutrophils (PMNs).
- Assessed histopathological changes, apoptosis markers (TUNEL, Bax, Bcl-2, caspase-3), inflammatory cytokines (IL-6, IL-8, IL-10), and p-GSK-3β levels.
Main Results:
- MIRI significantly increased lung injury, inflammation (IL-6, IL-8), and apoptosis (Bax, cleaved caspase-3), while decreasing IL-10 and p-GSK-3β.
- Ischemic post-conditioning reversed these MIRI-induced changes.
- Inhibition of GSK-3β abolished the protective effects of ischemic post-conditioning.
Conclusions:
- MIRI induces ALI through inflammation and apoptosis.
- Ischemic post-conditioning protects against ALI following MIRI by upregulating p-GSK-3β.
- GSK-3β modulation is a potential therapeutic target for MIRI-induced ALI.
