NBP Relieves Cardiac Injury and Reduce Oxidative Stress and Cell Apoptosis in Heart Failure Mice by Activating Nrf2/HO-1/Ca2+-SERCA2a Axis

Author:

Wang Zhongyu1ORCID,Zhang Yan2ORCID,Wang Lei3ORCID,Yang Chun4ORCID,Yang Hongliang1ORCID

Affiliation:

1. Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China

2. School of Public Health, Beihua University, Jilin 132033, China

3. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China

4. College of Basic Medicine, Beihua University, Jilin 132033, China

Abstract

Although heart failure (HF) has become one of the most fatal diseases in the whole world, there are fewer drugs for its treatment. Therefore, we focused on the protective effect of Dl-3-n-butylphthalide (NBP) on myocardial injury and oxidative stress in heart failure mice and further investigated the relationship with the Nrf2/HO-1/Ca2+-SERCA2a axis. Methods. C57BL/6J mice were divided into the sham group (Sham), heart Failure model group (HF), HF + NBP group (HN), HN + Nrf2 inhibitor (HNM), HN + Calmodulin-dependent protein kinase II (CaMKII) antagonist, KN93 (HNK). The HF mice model was prepared using abdominal aorta ligation. Mice’s heart function was accessed by echocardiography. Hematoxylin-eosin staining and MASSON staining were used to identify myocardial injury; the cell apoptosis was determined by the TUNEL staining assay. The expression of oxidative stress-related proteins was detected by the ELISA assay. The reactive oxygen species and Nrf2 expression in heart tissue were observed with the immunofluorescence assay. SERCA2a, calmodulin, endoplasmic reticulum stress regulatory proteins, and Nrf2/HO-1 in mice’ heart tissues were measured using Western blotting. Results. Moreover, NBP could significantly promote heart failure mice’s heart function, relieve the injury and inhibit cell apoptosis. Meanwhile, it could reduce ERS injury of heart failure mice through increasing SERCA2a level and reducing Ca2+ influx. NBP was demonstrated to minimize CaMKII phosphorylation level and decrease cAMP-response element-binding protein phosphorylation level, suggesting NBP could also activate the Nrf2/HO-1 signaling pathway. Conclusions. We demonstrated that NPBs treatment promotes the cardiomyocyte’s ERS and alleviates myocardial injury in heart failure mice, related to stimulating the Nrf2/HO-1 signaling pathway, regulating Ca2+-SERCA2a, and reducing Ca2+ influx.

Funder

Enterprise Fund

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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