Abstract:
AIM To clarify the role and mechanism of irisin in diabetic cardiomyopathy.
METHODS Mice were randomly divided into 4 groups: NS group, Irisin group, DCM group, and DCM-Irisin group. For in vitro experiments, mice were divided into HG/HF group, HG/HF-Irisin group, HG/HF-Irisin-Nrf2 inhibitor group, HG/HF-Nrf2 inhibitor group, HG/HF-Nrf2 agonist group, HG/HF-Nrf2 agonist-Sirt3 inhibitor group, and HG/HF-Irisin-Sirt3 inhibitor group. The expressions of autophagy and apoptosis-related proteins were detected by Western blot and RT-PCR, cell viability was detected by CCK-8, mitochondrial function was detected by MMP and ATP, and cell apoptotic rate was detected by TUNEL staining.
RESULTS The expressions of irisin protein and mRNA levels were decreased significantly in myocardial tissue of diabetic mice and HG/HF-induced H9c2 cells (P<0.05), while the expressions of LC3II/I and Cleaved caspase3 were increased significantly (P<0.01), and the protein expression of Nrf2 and P62 were decreased significantly (P<0.01). Irisin treatment partially alleviated the cardiomyocytes injury caused by DCM. The administration of Nrf2 inhibitor ML385 partially offset the protective effect of irisin, and significant inhibition of Sirt3 protein expression was observed (P<0.01). Under the condition of HG/HF, inhibiting Sirt3 activity eliminated the beneficial effect of Nrf2 up-regulation on H9c2 cells.
CONCLUSION Irisin mitigates the cardiomyocyte injury induced by DCM via activating Nrf2/Sirt3 signaling pathway.
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