Pemafibrate suppresses oxidative stress and apoptosis under cardiomyocyte ischemia‑reperfusion injury in type 1 diabetes mellitus

Li,Wei; Xu,Jianxin; Guo,Xin; Xia,Xinhua; Sun,Yanling

doi:10.3892/etm.2021.9762

Pemafibrate suppresses oxidative stress and apoptosis under cardiomyocyte ischemia‑reperfusion injury in type 1 diabetes mellitus

Authors:
- Wei Li
- Jianxin Xu
- Xin Guo
- Xinhua Xia
- Yanling Sun
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Affiliations: Third Medical Department, Tianjin Teda Hospital, Tianjin 300457, P.R. China, Nursing Department, Tianjin Teda Hospital, Tianjin 300457, P.R. China
Published online on: February 8, 2021 https://doi.org/10.3892/etm.2021.9762
Article Number: 331
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetes mellitus accelerates the hyperglycemia susceptibility‑induced injury to cardiac cells. The activation of peroxisome proliferator‑activated receptor α (PPARα) decreases ischemia‑reperfusion (IR) injury in animals without diabetes. Therefore, the present study hypothesized that pemafibrate may exert a protective effect on the myocardium in vivo and in vitro. A type 1 diabetes mellitus (T1DM) rat model and H9c2 cells exposed to high glucose under hypoxia and reoxygenation treatments were used in the present study. The rat model and the cells were subsequently treated with pemafibrate. In the T1DM rat model, pemafibrate enhanced the expression of PPARα in the diabetic‑myocardial ischemia‑reperfusion injury (D‑IRI) group compared with the D‑IRI group. The infarct size in the D‑IRI group was reduced following pemafibrate treatment relative to the untreated group. The disruption of the mitochondrial structure and myofibrils in the D‑IRI group was partially recovered by pemafibrate. In addition, to evaluate the mechanism of action of pemafibrate in the treatment of diabetic myocardial IR injury, an in vitro model was established. PPARα protein expression levels were reduced in the high glucose and hypoxia/reoxygenation (H/R) groups compared with that in the control or high glucose‑treated groups. Pemafibrate treatment significantly enhanced the ATP and superoxide dismutase levels, and reduced the mitochondrial reactive oxygen species and malondialdehyde levels compared with the high glucose combined with H/R group. Furthermore, pemafibrate inhibited the expression of cytochrome c and cleaved‑caspase‑3, indicating its involvement in the regulation of mitochondrial apoptosis. Pemafibrate also reduced the expression of nuclear factor‑κB (NF‑κB), the activation of which reversed the protective effects of pemafibrate on diabetic myocardial IR injury in vitro. Taken together, these results suggested that pemafibrate may activate PPARα to protect the T1DM rat myocardium against IR injury through inhibition of NF‑κB signaling.

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