CACNB1 alleviates mepivacaine‑induced myocardial ischemia/reperfusion injury by promoting Nrf2 nuclear translocation

Myocardial ischemia/reperfusion injury (MIRI) is a challenging Cardiovascular Disease. Mepivacaine, a common local anesthetic, exacerbates myocardial injury during ischemia‑reperfusion (IR). Understanding the underlying mechanisms of MIRI and potential therapeutic targets is important to treat this disease. In the present study, differentially expressed genes (DEGs) from the GSE19339 dataset were identified and analyzed. The expression of calcium voltage‑gated channel auxiliary subunit β1 (CACNB1) was measured in myocardial infarction samples and the effects of different doses of mepivacaine on cell cycle progression, Apoptosis, cell viability, inflammatory response and oxidative stress were evaluated in H9c2 cells. Hypoxia‑reoxygenation (H/R) treatment simulated MIRI, highlighting the role of CACNB1 in mepivacaine‑induced cellular inflammation and injury. The present study identified 2,396 upregulated and 1,230 downregulated DEGs enriched in pathways such as inflammatory response and chemokine signaling. Mepivacaine induced Apoptosis, G₁ phase arrest and increased oxidative stress markers, including elevated ROS and MDA levels together with decreased SOD activity, as well as inflammatory cytokines (TNF‑α, IL‑1β and IL‑6), in a dose‑dependent manner in H9c2 cells. CACNB1 knockdown reduced mepivacaine‑ and H/R‑induced damage, inhibiting inflammation and Apoptosis via the CACNB1/NOD‑like receptor protein 3 (NLRP3)/Nuclear factor erythroid 2‑related factor 2 (Nrf2) axis. Furthermore, CACNB1 knockdown enhanced Nrf2 nuclear translocation, indicating a stress response mechanism. Mepivacaine exacerbated MIRI by inducing Apoptosis, G₁ phase arrest, oxidative stress and inflammation in H9c2 cells. CACNB1 knockdown reduced these effects. Targeting the CACNB1/NLRP3/Nrf2 axis may be a potential strategy for mitigating myocardial injury caused by mepivacaine and IR.

calcium voltage‑gated channel auxiliary subunit β 1; mepivacaine; myocardial ischemia/reperfusion injury; nuclear factor erythroid 2‑related factor 2; nuclear translocation.