Metformin Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by Modulating JNK Pathway and Inhibiting...

Area of Science:

• Cardiovascular Research
• Pharmacology
• Cellular Biology

Background:

• Myocardial ischemia-reperfusion injury (MIRI) exacerbates heart damage upon reperfusion.
• Metformin (Met), an antidiabetic drug, exhibits cardioprotective effects via anti-inflammatory, antiapoptotic, and metabolic regulation.
• The study focuses on Metformin's impact on the JNK pathway and PANoptosis in MIRI.

Purpose of the Study:

• Investigate Metformin's cardioprotective effects in a rat MIRI model.
• Elucidate Metformin's modulation of the c-Jun N-terminal kinase (JNK) pathway.
• Determine Metformin's role in inhibiting PANoptosis mechanisms.

Main Methods:

• Triphenyl tetrazole chloride (TTC) and Wheat germ agglutinin (WGA) staining assessed myocardial infarction and hypertrophy.
• ELISA measured serum injury markers and inflammatory cytokines.
• Immunofluorescence and Western blotting evaluated PANoptosis and JNK pathway involvement.

Main Results:

• Metformin significantly reduced myocardial injury area and infarct size.
• Metformin lowered serum levels of cardiac biomarkers (c-TnI, CK-MB, LDH), inflammatory cytokines (IL-6, TNF-α), and reactive oxygen species (ROS).
• Metformin attenuated MIRI-induced PANoptosis by inhibiting JNK phosphorylation and reducing ROS, an effect reversed by anisomycin.

Conclusions:

• Metformin's cardioprotective effect in MIRI is mediated by regulating the JNK pathway and inhibiting PANoptosis.
• Metformin demonstrates potential as a therapeutic agent for myocardial ischemia-reperfusion injury.
• Targeting the JNK pathway is crucial for Metformin's protective action in MIRI.