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| Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway |
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| KeyWord:Chinese medicine, Danshensu, ischemia reperfusion injury, Sirt1/FoxO1/Rab7 signal pathway, reactive oxygen species, apoptosis |
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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 μ mol/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), cardiac troponin T (cTnT), reactive oxygen species (ROS), superoxide dismutase (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 (cTnT, 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 SOD and GSH-PX. 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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