Ultrasound-targeted semaglutide-loaded PEG-nanoliposomes microbubble destruction protects diabetic cardiomyopathy by activating PI3K/Akt/Nrf2 signaling pathway

Figures

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  Fig. 1. Characterization of Sem-PEG-lips. (A) Visual observation, (B) scanning electron microscopy, (C) particle size distribution and (D) zeta potential of Sem-PEG-lips.

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  Fig. 2. Effects of UTMD combined Sem-PEG-lips on diabetic symptoms in DCM rats. (A) Random plasma glucose, (B) fasting plasma glucose, (C) HbA1c%, and (D) body weight of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group.

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  Fig. 3. Effects of UTMD combined Sem-PEG-lips on myocardial injury in DCM rats. (A) Representative images of H&E stain in myocardial tissue (Scale bars ( × 200): 100 μm), and serum levels of (B) CTnl, (C) LDH, and (D) CK-MB of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.

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  Fig. 4. Effects of UTMD combined Sem-PEG-lips on cardiac functions of the DCM rats. (A) LVEDD, (B) LVESD, (C) LVEDV, (D) LVESV, (E) LVEF and (F) LVFS in DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.

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  Fig. 5. Effects of UTMD combined Sem-PEG-lips on myocardial fibrosis in DCM rats. (A) Representative images of Masson stain (Scale bars ( × 200): 100 μm) and the contents of (B) Collagen I, (C) Collagen III, and (D) TGF-β1 in myocardial tissue of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.

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  Fig. 6. Effects of UTMD combined Sem-PEG-lips on oxidative stress in DCM rats. Quantitative analysis of (A) MDA contents and the activities of (B) SOD, (C) GSH-Px, and (D) CAT in myocardial tissue of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.

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  Fig. 7. Effects of UTMD combined Sem-PEG-lips on expression of PI3K/Akt/Nrf2 signaling pathway in myocardial tissue of DCM rats. (A) Representative images and expression levels of (B) PI3K and (C) p-Akt/Akt in myocardial tissue of DCM rats after consecutive 12 weeks intervention; (D) Representative images and expression levels of (E) Nrf2, (F) SOD2, and (G) NQO1 in myocardial tissue of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 5. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.

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  Fig. 8. Inhibition of PI3K/Akt axis on beneficial effect of UTMD combined Sem-PEG-lips in DCM rats. (A) Western blot representative images and expression levels of (B) PI3K and (C) p-Akt/Akt, (D) H&E scores, (E) fibrosis% of Masson stain in myocardial tissue, and the serum levels of (F) CTnl, (G) LDH and (H) CK-MB of DCM rats after consecutive 12 weeks intervention. Data presented as Mean ± SD, n = 10. *p < 0.05, **p < 0.01, ***p < 0.001 vs. DCM group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. UTMD + Sem-PEG-lips group.