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

Figure 7

PPARγ is essential for the protective effects of NOB against cardiac remodeling after MI. (a) Masson’s trichrome staining of the peri-infarct area indicated increased heart fibrosis following PPARγ inhibitor injection compared with the NOB intervention group (, 6, 7, and 6). (b) The protein expression of collagen I and α-SMA was significantly increased after PPARγ inhibitor injection ( per group). (c) Increased mRNA expression levels of collagen I and collagen III also indicated fibrosis ( per group). (d) The expression levels of ANP and BNP were significantly elevated in the inhibitor group ( per group). (e) HE and WGA staining showed the enlargement of the cross-sectional area in the inhibitor group (scale bars: 50 μm and , 6, 7, and 6 for HE staining; scale bars: 20 μm and per group for WGA staining). (f) The ratio of Bax/Bcl2 and the expression of cleaved caspase-3 were both higher in the inhibitor group than in the NOB intervention group ( per group for Bax/Bcl2 and per group for cleaved caspase-3). (g) TUNEL staining showed that the apoptosis-positive cardiomyocyte rate was upregulated in the PPARγ inhibitor group compared with the NOB intervention group (scale bars: 100 μm, per group). (h) The protein expression level of PPARγ and PGC1α decreased after PPARγ inhibitor injection ( per group). (i) WB analysis showed that the expression of Nrf-2 and HO-1 was downregulated in the MI group and upregulated following NOB intervention; the PPARγ inhibitor injection abolished the upregulated expression of Nrf-2 and HO-1 ( per group). Data are presented as . ; ; . PPARγ: peroxisome proliferator-activated receptor gamma; NOB: nobiletin; ANP: natriuretic peptide type A; BNP: natriuretic peptide B; HE staining: haematoxylin and eosin staining; WGA staining: wheat germ agglutinin staining; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling; PGC1α: PPARγ coactivator 1α; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase 1.

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