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Research Paper|Volume 16, Issue 8|pp 6937—6953

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats

Ya-Nan Cui1, Na Tian2,4, Yan-Hai Luo3, Ji-Jun Zhao2, Cheng-Fei Bi2,4, Yi Gou2,4, Jia Liu2, Ke Feng2, Jun-Fei Zhang2,4
  • 1Medical Records and Statistics Room, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
  • 2Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
  • 3Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
  • 4School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750000, China
* Equal contribution
Received: August 24, 2023Accepted: March 13, 2024Published: April 19, 2024
https://doi.org/10.18632/aging.205735

Copyright: © 2024 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aims: This study aimed to evaluate the effects of VC on SIMI in rats.

Methods: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways.

Results: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/β in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group.

Significance: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.