Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Figure 5

PPARγ inhibitor (T0070907) weakened the protective effects of NOB against hypoxia-induced apoptosis and PE-induced pathological cardiac hypertrophy in NRVMs. (a) In the hypoxia-induced apoptotic model, the expression levels of PPARγ and PGC1α were downregulated in the PPARγ inhibitor group compared with the NOB intervention group, confirming the inhibitor function ( per group). (b) In the hypoxia model, the combined intervention of NOB and PPARγ inhibitor (T0070907) increased the Bax/Bcl2 ratio compared with NOB intervention alone, whereas cointervention with both the NOB and PPARγ agonist (rosiglitazone) resulted in a Bax/Bcl2 ratio similar to that of the NOB group ( per group). (c) TUNEL staining showed reduced apoptosis in NRVMs in the NOB intervention group, but this effect was eliminated by the PPARγ inhibitor (blue: nuclear; red: α-actinin; and green: apoptotic-positive nuclear; scale bars: 100 μm, per group). (d) The results of immunofluorescence staining showed that the cell sizes of NRVMs were larger in the PPARγ inhibitor group, whereas PPARγ agonists failed to further shrink the cell size (blue: nuclear; green: α-actinin; scale bars: 100 μm, per group). (e) The expression of ANP and BNP increased in the PPARγ inhibitor group ( per group). Data are presented as . ; ; ; ^ns. PPARγ: peroxisome proliferator-activated receptor gamma; NOB: nobiletin; NRVMs: neonatal rat ventricular cardiomyocytes; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling; PGC1α: PPARγ coactivator 1α; ANP: natriuretic peptide type A; BNP: natriuretic peptide B.

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