Sevoflurane reduced myocardial injury in rat and cell ischemia-reperfusion models through a circ_SMG6-related pathway

A preclinical study reported that sevoflurane reduced myocardial injury in a rat model of myocardial ischemia-reperfusion injury (MIRI) and in human cardiomyocyte models subjected to hypoxia and reoxygenation. The authors associated these effects with reduced circ_SMG6 expression and changes in TLR4/mTOR signaling, based on experiments summarized in the article abstract.

Researchers divided Sprague-Dawley rats into sham-operated, MIRI, and sevoflurane-plus-MIRI groups. They measured myocardial infarct size with 2,3,5-triphenyltetrazolium chloride staining, examined cardiac tissue with hematoxylin and eosin staining, and detected apoptotic nuclei using TUNEL staining. Quantitative reverse-transcription PCR and western blotting were used to quantify circ_SMG6 and TLR4/mTOR expression.

In the rat experiment, MIRI increased the myocardial apoptotic index, infarct size, and structural cardiac damage while elevating circ_SMG6 and TLR4/mTOR signaling. These changes were reduced with sevoflurane, although the abstract states that they were not entirely restored. In AC16 and HCM cardiomyocyte models, hypoxia-reoxygenation increased circ_SMG6, reduced cell viability, increased production of TNF-α, IL-1β, and IL-6, and increased the measured TLR4/mTOR signaling readout.

The investigators also tested circ_SMG6 overexpression and knockdown 48 hours before hypoxia-reoxygenation, with or without sevoflurane. Knockdown reversed the measured effects of hypoxia-reoxygenation, whereas overexpression further aggravated the reported injury, supporting the involvement of circ_SMG6 in the inflammatory and apoptotic responses in these cell models. Sevoflurane produced changes similar to circ_SMG6 silencing at the functional and signaling levels. These findings come from rat and cell experiments and do not establish clinical efficacy or safety in patients with myocardial infarction or MIRI; the assessment here is limited to the published abstract.

Subject of Research: Preclinical testing of sevoflurane, circ_SMG6, and TLR4/mTOR signaling in myocardial ischemia-reperfusion models

Article Title: Sevoflurane suppresses circ_SMG6 to inhibit TLR4/mTOR signaling and attenuate myocardial ischemia-reperfusion injury

Article References: Feng, M., Li, W., Chen, B., & Sun, Y. (2026). Sevoflurane suppresses circ_SMG6 to inhibit TLR4/mTOR signaling and attenuate myocardial ischemia-reperfusion injury. Molecular Biology Reports, 53(1), Article 1590. https://doi.org/10.1007/s11033-026-12758-y

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12758-y

Keywords: sevoflurane, myocardial ischemia-reperfusion injury, circ_SMG6, TLR4/mTOR signaling, cardioprotection, Sprague-Dawley rats, cardiomyocytes, hypoxia-reoxygenation, inflammation, apoptosis, suppresses, circ