High mRNA Expression of 24 Dehydrocholesterol Reductase (DHCR24) in the Treatment of Doxorubicin-Induced Heart Failure in Rats

Figures

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  Figure 1. LNP-DHCR24-mRNA in the treatment of heart failure.

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  Figure 2. Characterization of the zeta potential and particle size distribution of LNP-DHCR24-mRNA: (A) zeta potential, which is used to observe the stability of LNPs; (B) particle size distribution and observed concentration of LNP size.

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  Figure 3. Transmission electron microscope characterization of DHCR24-mRNA (A) and LNP-DHCR24-mRNA (B).

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  Figure 4. The mRNA and protein levels of DHCR24 in each administration group of H9C2 rat cardiomyocytes: (A) qPCR results for DHCR24 mRNA; (B) protein results of DHCR24-mRNA. Data are expressed as the mean ± SD. ** p < 0.01 compared to the blank group.

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  Figure 5. Comparison of the mortality rate and 6-min walk test results for each treatment group with those of the model group: (A) mortality rate of each group; (B) number of turns for each group. Data are expressed as the mean ± SD. * p < 0.05 and ** p < 0.01 compared to the model group.

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  Figure 6. Body weight of each group of rats before and after modeling, as well as before and after administration: (A) weight during the modeling and treatment periods; (B) weight of the model at four weeks of construction; (C) weight at the time of treatment for four weeks. Data are expressed as the mean ± SD. * p < 0.05 and *** p < 0.005compared to the blank or model group.

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  Figure 7. Tibia length of each group of rats and the ratio of each tissue to tibia length: (A) tibia length; (B) ratio of heart weight to tibia length; (C) ratio of liver weight to tibia length; (D) ratio of spleen weight to tibia length; (E) ratio of lung weight to tibia length; (F) ratio of brain weight to tibia length. Data are expressed as the mean ± SD. ns, not significant; ** p < 0.01 and *** p < 0.001 compared to the model group.

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  Figure 8. Histopathological changes in heart tissue in heart failure rat model using HE staining. The red arrows mark the areas of myocardial necrosis, the green arrows mark the areas of myocardial hypertrophy, and the blue arrows mark the areas of inflammatory cell infiltration.

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  Figure 9. Expression of DHCR24 in cardiac tissue and the effects of administration of DHCR24-mRNA on the protein expression levels of PRDX2, Sirt3, and TRX1 in the tissues of rats with heart failure: (A) protein expression of DHCR24 within cardiac tissue; (B) protein expression of PRDX2 within cardiac tissue; (C) protein expression of Sirt3 within cardiac tissue; (D) protein expression of TRX1 within cardiac tissue. Data are expressed as the mean ± SD. * p < 0.05 and ** p < 0.01 compared to the blank or model group.

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  Figure 10. Effects of administration of DHCR24-mRNA on the expression of IL-1β, IL-10, VEGF, NT-proBNP, and BNP in the blood of rats with heart failure: (A) expression of IL-1β in the blood of rats from each group; (B) expression of IL-10 in the blood of rats from each group; (C) expression of VEGF in the blood of rats from each group; (D) expression of NT-proBNP in the blood of rats from each group; (E) expression of BNP in the blood of rats from each group. Data are expressed as the mean ± SD. * p < 0.05 and ** p < 0.01 compared to the blank or model group.

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  Figure 11. The B-ultrasound situation of each group of rats on the 27th day after administration of DHCR24-mRNA. The red dotted line and the green dotted line represent the distances of the left ventricular cavity during diastole and systole respectively. Data are expressed as the mean ± SD. * p < 0.05 and ** p < 0.01 compared to the blank or model group.

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  Figure 12. TEM image of heart tissues of each group of rats: (A) results of the blank group; (B) results of the model group; (C) results of the mRNA stock solution intravenous injection group; (D) results of the mRNA stock solution cardiac injection group; (E) results of the LNP-mRNA stock solution intravenous injection group; (F) results of the LNP-mRNA stock solution cardiac injection group. The blue arrow indicates the Z-line of the I-band of myocardial cells; the green arrow represents the M-line of the A-band; the black arrow shows the myofilament; the red arrow stands for the swelling of some mitochondria; the orange arrow represents the rupture of the membranes of some mitochondria; the yellow arrow symbolizes the autophagosome.