Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat

Figures

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  Figure 1. Notopterol improves mortality rate in pulmonary arterial hypertension rats. Kaplan–Meier survival curves in the group (n = 10 for each group).

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  Figure 2. Notopterol improves right ventricular function and reduces right ventricular systolic pressure in pulmonary arterial hypertension rats. (A) The right ventricular pressure waveform. Quantification of RVSP, (B) PAT, (C) PET, (D) PAT/PET, (E) LVEF, (F) 3 weeks after MCT injection (n = 8 for each group); *p < 0.05, **p < 0.01, ***p < 0.001. MCT, monocrotaline; Veh, vehicle; PAT, pulmonary blood flow acceleration time; PET, pulmonary ejection time; PAT/PET, pulmonary blood flow acceleration time/ pulmonary ejection time; RVSP, right ventricular systolic pressure.

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  Figure 3. Notopterol reduces right ventricular hypertrophy and fibrosis in pulmonary arterial hypertension rats. (A) Quantification of Masson staining; (B) Representative histopathological images of RV sections with Masson staining for collagen deposition (40 ×); (C) Quantification of Myocyte area; (D) Myocyte area. Representative cross-section cardiomyocytes (40 ×); (E) RV hypertrophy index; (F) RV mRNA expression of collagen I. (n = 8 for each group); *p < 0.05, **p < 0.01, ***p < 0.001. IVS, interventricular septum; LV, left ventricle.

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  Figure 4. Notopterol eases pulmonary vascular remodeling. (A) Representative H&E staining micrograph of lung tissue sections (100 ×); (B) Quantification of the medial wall thickness of the small pulmonary arteries (n = 8 for each group); (C) Expression of α-SMA in lungs evaluated with immunohistochemistry staining (100 ×); (D) Quantification of the arteries muscularization of the small pulmonary arteries (n = 8 for each group); (E) Western blots of PCNA in lungs; (F) Quantification of PCNA expression in the lungs. (n = 4 for each group). *p < 0.05, **p < 0.01, ***p < 0.001. H&E, hematoxylin-eosin; α-SMA, α-smooth muscle actin; PCNA, proliferating cell nuclear antigen.

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  Figure 5. Notopterol attenuates the pro-inflammatory factors in the lungs of PAH rats. (A) Western blots of IL-1β and IL-6 in lungs; (B) Quantification of IL-1β expression in the lungs (n = 8 for each group); (C) Quantification of IL-6 expression in the lungs (n = 8 for each group). *p < 0.05, ***p < 0.001.

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  Figure 6. Notopterol inhibits the proliferation and migration of human pulmonary artery smooth muscle cells in response to hypoxia in vitro. (A) Representative images of the EdU assay of HPASMCs in vitro (100 ×); (B) Quantification of the EdU assay of HPASMCs; (C) CCK-8 assay of HPASMCs; (D) Representative images of the wound healing assay of HPASMCs in vitro; (E) Quantification of the wound healing assay of HPASMCs; (n = 3, biological replicates; three wells each time for the EdU assay, six wells each time for the CCK-8 assay, three wells each time for the wound healing assay). *p < 0.05, **p < 0.01, ***p < 0.001. EdU, 5-ethynyl-2′-deoxyuridine; HPASMCs, human pulmonary arterial smooth muscle cells; CCK-8, Cell Counting Kit-8.