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Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway

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Abstract

Objective

To explore the specific molecular mechanisms of Danshensu (DSS) in the treatment of ischemia reperfusion injury (IRI).

Methods

IRI model was established with isolated rat hearts by performing global ischaemia for 30 min, and then followed by 60 min reperfusion. Also, H9C2 cells were subjected to 4-h hypoxia followed by 3-h reoxygenation. Then 10 μmol/L DSS were added in the reperfusion/reoxygenation step to intervene IRI. Cardiac function, structural change and apoptosis were respectively tested by Langendorff System, hematoxylin and eosin (HE) and terminal-deoxynucleotidyl transferase mediated nick endabeling (TUNEL) stainings. Then lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide gasification enzyme (SOD) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay (ELISA). Sirt1/FoxO1/Rab7 Signal Pathway was monitored at both protein and mRNA levels.

Results

The results showed that IRI not only greatly attenuated cardiac function (LVDP and ±dp/dtmax, P<0.01, P<0.05) and increased the level of the marker enzymes (cardiac troponin T, LDH, P<0.01) from the coronary effluents, but also markedly induced changes in the structure of cardiomyocytes and contributed to apoptosis, which were mediated by boosted endogenous ROS. However, after treatment with DSS all above indexes were improved, which was related to activating Sirt1/FoxO1/Rab7 signal pathway accompanied with the enhancement of antioxidant defense system, such as superoxide gasification enzyme and glutathione peroxidase.

Conclusion

DSS is able to protect hearts from IRI, which may be attributable to inhibiting excessive ROS through Sirt1/FoxO1/Rab7 signaling.

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Acknowledgement

The authors are grateful for facility and field assistance from the Tianjin University of Traditional Chinese Medicine.

Author information

Authors and Affiliations

  1. Department of Neurology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China

    Da-wei Sun

  2. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Qing Gao

  3. Department of Cardiology, Tianjin Union Medical Center, Tianjin, 300121, China

    Xin Qi

Authors
  1. Da-wei Sun
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  2. Qing Gao
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  3. Xin Qi
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Contributions

Qi X designed experiments; Sun DW and Gao Q carried out experiments, analyzed experimental results, sequencing data and wrote the manuscript.

Corresponding author

Correspondence to Xin Qi.

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The authors confirm that there are no conflicts of interest.

Additional information

Supported by Science and Technology Planning Projects of Science and Technology Commission of Tianjin (No. 18ZXDBSY00080), National Natural Science Foundation of China (No. 81503504), and Key Medical and Health Projects of Health and Family Planning Commission of Tianjin (No. 2015KG110)

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Sun, Dw., Gao, Q. & Qi, X. Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway. Chin. J. Integr. Med. 26, 283–291 (2020). https://doi.org/10.1007/s11655-019-3165-9

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  • DOI: https://doi.org/10.1007/s11655-019-3165-9

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