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

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.

• Authors: Da-Wei Sun, Qing Gao, Xin Qi
• Journal: Chinese journal of integrative medicine (Chin J Integr Med) Vol. 26 Issue 4 Pg. 283-291 (Apr 2020) ISSN: 1672-0415 [Print] China
• PMID: 31254156 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Lactates
• Nerve Tissue Proteins
• rab7 GTP-Binding Proteins
• rab7 GTP-binding proteins, rat
• Foxo1 protein, rat
• 3,4-dihydroxyphenyllactic acid
• L-Lactate Dehydrogenase
• Sirt1 protein, rat
• Sirtuin 1
• rab GTP-Binding Proteins

Topics

• Animals
• Antioxidants (pharmacology)
• Disease Models, Animal
• Ischemia
• L-Lactate Dehydrogenase (metabolism)
• Lactates (pharmacology)
• Myocytes, Cardiac (drug effects, metabolism)
• Nerve Tissue Proteins
• Oxidative Stress (drug effects)
• Rats
• Reperfusion Injury (drug therapy, metabolism)
• Signal Transduction (drug effects)
• Sirtuin 1 (drug effects)
• rab GTP-Binding Proteins (drug effects)
• rab7 GTP-Binding Proteins