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Remote Ischemic Postconditioning Inhibited Mitophagy to Achieve Neuroprotective Effects in the Rat Model of Cardiac Arrest

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Abstract

Remote ischemic postconditioning (RI-postC) is an effective measure to improve nerve function after cardiac arrest. However, the brain protective mechanism of RI-postC has not been fully elucidated, and whether it is related to mitophagy is unclear. In this study, we used the rat model of cardiac arrest to study the effect of RI-postC on mitophagy and explore its possible signaling pathways. Rats were randomly divided into Sham group, CA/CPR group, Mdivi-1 group and RI-postC group. The animal model of cardiac arrest was established by asphyxia. RI-postC was performed by clamping and loosening the left femoral artery. Mdivi-1 was treated with a single intravenous injection. Levels of TOMM20, TIM23, Mfn1, PINK1 and parkin were detected by western blots. Mitochondrial membrane potential was measured by flow cytometry. Real-time PCR was used to detect relative mitochondrial DNA levels. The apoptosis of hippocampal neurons was detected by flow and TUNEL. In addition, Histopathological tests were performed. The results showed that RI-postC was similar to the mitophagy inhibitor Mdivi-1, which could inhibit the decrease of mitophagy-related protein level, improve mitochondrial membrane potential and up-regulate the ratio of mt-Atp6/Rpl13 after cardiopulmonary resuscitation (CPR). Furthermore, RI-postC could also reduce the rate of hippocampal nerve apoptosis and the damage of hippocampal neurons after CPR. Moreover, RI-postC and Mdivi-1 could reduce the protein levels of PINK1 and parkin in mitochondria after CPR, while increasing PINK1 levels in the cytoplasm. These findings suggested that RI-postC could inhibit the overactivation mitophagy through the PINK1/parkin signaling pathway, thus providing neuroprotective effects.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant numbers 81471831 and 81901932). Thanks to the Laboratory of cardiac surgery of Tongji Medical College of HuaZhong University of Science and Technology for the experimental equipment support and technical guidance.

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Authors and Affiliations

  1. The First School of Clinical Medical, Southern Medical University, Guangzhou, China

    Yang Huang, ZhiTian Tan & ShuiBo Zhu

  2. Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command, Wuluo road, 627#, Wuhan, 430070, Hubei, China

    Yang Huang, Xuhui Gao, Yu Zhang, ZhiTian Tan & ShuiBo Zhu

  3. Department of Anesthesiology, General Hospital of Central Theater Command, Wuhan, China

    Xiang Zhou

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  1. Yang Huang
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Correspondence to ShuiBo Zhu.

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Huang, Y., Gao, X., Zhou, X. et al. Remote Ischemic Postconditioning Inhibited Mitophagy to Achieve Neuroprotective Effects in the Rat Model of Cardiac Arrest. Neurochem Res 46, 573–583 (2021). https://doi.org/10.1007/s11064-020-03193-x

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  • DOI: https://doi.org/10.1007/s11064-020-03193-x

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