Department of Biological and Biomedical Sciences, Aga Khan University, Karachi Pakistan.
Department of Physiology, Rashid Latif Khan University Medical College, Lahore, Pakistan.
PLoS One. 2024 Mar 15;19(3):e0299503. doi: 10.1371/journal.pone.0299503. eCollection 2024.
Myocardial infarction (MI) is a leading cause of morbidity and mortality in the world and is characterized by ischemic necrosis of an area of the myocardium permanently devoid of blood supply. During reperfusion, reactive oxygen species are released and this causes further insult to the myocardium, resulting in ischemia-reperfusion (IR) injury. Since Nrf2 is a key regulator of redox balance, it is essential to determine its contribution to these two disease processes. Conventionally Nrf2 levels have been shown to rise immediately after ischemia and reperfusion but its contribution to disease process a week after the injury remains uncertain. Mice were divided into MI, IR injury, and sham surgery groups and were sacrificed 1 week after surgery. Infarct was visualized using H&E and trichrome staining and expression of Nrf2 was assessed using immunohistochemistry, Western blot, and ELISA. MI displayed a higher infarct size than the IR group (MI: 31.02 ± 1.45%, IR: 13.03 ± 2.57%; p < 0.01). We observed a significantly higher expression of Nrf2 in the MI group compared to the IR model using immunohistochemistry, spot densitometry of Western blot (MI: 2.22 ± 0.16, IR: 1.81 ± 0.10, Sham: 1.52 ± 0.13; p = 0.001) and ELISA (MI: 80.78 ± 27.08, IR: 31.97 ± 4.35; p < 0.01). There is a significantly higher expression of Nrf2 in MI compared to the IR injury group. Modulation of Nrf2 could be a potential target for therapeutics in the future, and its role in cardioprotection can be further investigated.
心肌梗死（MI）是全球发病率和死亡率的主要原因，其特征是心肌的一个区域由于缺血而永久丧失血液供应导致的坏死。在再灌注期间，活性氧会被释放，这会对心肌造成进一步的损伤，导致缺血再灌注（IR）损伤。由于 Nrf2 是氧化还原平衡的关键调节因子，因此确定其对这两种疾病过程的贡献至关重要。传统上，已经表明 Nrf2 水平在缺血和再灌注后立即升高，但它对损伤后一周的疾病过程的贡献仍然不确定。将小鼠分为 MI、IR 损伤和假手术组，并在手术后 1 周处死。使用 H&E 和三色染色观察梗死，使用免疫组化、Western blot 和 ELISA 评估 Nrf2 的表达。MI 组的梗死面积明显大于 IR 组（MI：31.02±1.45%，IR：13.03±2.57%；p<0.01）。与 IR 模型相比，我们在 MI 组中观察到 Nrf2 的表达明显更高，免疫组化、Western blot 点密度（MI：2.22±0.16，IR：1.81±0.10，Sham：1.52±0.13；p=0.001）和 ELISA（MI：80.78±27.08，IR：31.97±4.35；p<0.01）。与 IR 损伤组相比，MI 中 Nrf2 的表达明显更高。Nrf2 的调节可能是未来治疗的一个潜在靶点，可以进一步研究其在心脏保护中的作用。
