LuQi Formula relieves ventricular remodeling through improvement of HIF-1α-mediated intestinal barrier integrity

Figures

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  Fig. 1. LQF relieves ventricular remodeling after AMI in vivo. A Ventricular remodeling was constructed in Wistar rats and randomly divided into 4 groups (for all groups, n = 6). Rats were administered by gavage with LQF (dry powder, 315 mg/kg, equal to clinical dose for human) or BNZ (10 mg/kg) for 4 weeks. B Plasma BNP content (ng/L). C Cardiac function indexes LVEF and LVFS of rats were measured with echocardiography. D H&E and Masson’s trichrome staining of the infarcted area of heart (scale bar = 1 mm, and for the zoom, scale bar = 0.5 mm). Three views were randomly selected from each slice (n = 6 for each group) and the blue collagen area of each slice was quantitatively analyzed using ImageJ software. The average blue collagen area of the model group was calibrated to a value ‘one’, and the remaining groups were analyzed relative to the model group. E TUNEL staining of the infarcted area of heart (scale bar = 20 μm). Three views were randomly selected from each slice (n = 6 for each group) and fluorescence intensity of each slice was quantitatively analyzed using ImageJ software. The average fluorescence intensity of the model group was calibrated to a value ‘one’, and the…

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  Fig. 2. LQF maintains intestinal barrier integrity in ventricular remodeling rats. A H&E (scale bar = 200 μm) and AB-PAS staining (scale bar = 200 μm) of colon (for all groups, n = 6). B Plasma LPS (ng/L), D-lactate (μg/L) and zonulin (ng/L) content in rats. C Serum TNF-α (ng/L), IL-1β (ng/L) content in rats. D Immunofluorescence of Occluding, Claudin-1, ZO-1 of colon (scale bar = 50 μm). Three views were randomly selected from each slice (n = 6 for each group) and the fluorescence intensity of each slice was quantitatively analyzed using ImageJ software. The average fluorescence intensity of the model group was calibrated to a value ‘one’, and the remaining groups were analyzed relative to the model group. E Protein expression of Occluding, Claudin-1 and HIF-1α of colon. β-actin served as a loading control. Three samples were randomly selected from each group for target protein detection, and the grayscale values of each band were quantitatively analyzed using ImageJ software. The average grayscale value of the model group was calibrated to a value ‘one’, and the remaining groups were analyzed relative to the model group. F Immunohistochemistry of HIF-1α of colon (scale bar = 50 μm).…

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  Fig. 3. LQF maintains intestinal barrier integrity by upregulating HIF-1α in colon. A Ventricular remodeling was constructed in Wistar rats and randomly divided into 4 operated groups, and set up a sham-operated group as a control (for 2ME group, n = 4, 2ME + LQF group, n = 5, other groups, n = 6). Rats were administrated by gavage with LQF alone (315 mg/kg) or intraperitoneally administrated with 2ME (15 mg/kg) or both for 4 weeks. B H&E (scale bar = 200 μm) and AB-PAS staining (scale bar = 200 μm) of the colon. C Plasma LPS (ng/L), D-lactate (μg/L), and zonulin (ng/L) content in rats were measured. D Serum TNF-α (ng/L), and IL-1β (ng/L) content in rats were measured. E, F Immunohistochemistry (scale bar = 50 μm) and protein expression of HIF-1α in the colon were shown. Three views were randomly selected from each slice (for 2ME group, n = 4, 2ME + LQF group, n = 5, other groups, n = 6) for target protein detection, the fluorescence intensity and grayscale values were quantitatively analyzed using ImageJ software. The fluorescence intensity and grayscale values of the model group were calibrated to a value ‘one’, respectively, and the remaining groups were analyzed relative to the model…

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  Fig. 4. LQF relieves ventricular remodeling partially through HIF-1α-mediated intestinal barrier integrity. A Cardiac function indexes, LVEF and LVFS levels of ventricular remodeling rats were measured with echocardiography (for 2ME group, n = 4, 2ME + LQF group, n = 5, other groups, n = 6). B H&E and Masson’s trichrome staining of the infarcted area of heart (scale bar = 1 mm, and for the zoom, scale bar = 0.5 mm). Three views were randomly selected from each slice (for 2ME group, n = 4, 2ME + LQF group, n = 5, other groups, n = 6) and the blue collagen area of each slice was quantitatively analyzed using ImageJ software. The average blue collagen area of the model group was calibrated to a value ‘one’, and the remaining groups were analyzed relative to the model group. C TUNEL of the infarcted area of heart (scale bar = 20 μm). Three views were randomly selected from each slice (for 2ME group, n = 4, 2ME + LQF group, n = 5, other groups, n = 6) and the fluorescence intensity of each slice was quantitatively analyzed using ImageJ software. The average fluorescence intensity of the model group was calibrated to a value ‘one’, and the remaining groups were analyzed relative to the model…

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  Fig. 5. LQF protects cardiac function potentially by regulating intestinal barrier integrity. A The cardiac function indexes LVEF, LVSV and plasma BNP content (pg/mL) of HF patients before and after LQF treatment (oral treatment for 2–4 months, with a daily dose equivalent to 107 g of raw drug). B Plasma LPS (EU/mL), D-lactate (μg/mL) and zonulin (ng/L) content of HF patients. * p < 0.05, *** p < 0.001 vs before treatment. n = 17