Bone marrow mesenchymal stem cell transplantation alleviates radiation-induced myocardial fibrosis through inhibition of the TGF-β1/Smad2/3 signaling pathway in rabbit model

Figures

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  Fig. 1. BMSCs improve cardiac function. The cardiac function was measured after irradiation. A. Images of heart ultrasound at 3 months after irradiation; B. LVEF: left ventricular ejection fraction; C. FS: fractional shortening; D. LVIDd: left ventricular internal diameter at end-diastole. E. LVIDs: left ventricular internal diameter at end-systole; Values are expressed as mean ± SD (n = 6 rabbits); ∗∗P < 0.01 and ∗∗∗P < 0.001vs Control; #P < 0.05, ##P < 0.01 and ###P < 0.001 vs RT.

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  Fig. 2. BMSCs reduce myocardial damage. The electrocardiography was measured after irradiation. A. Images of electrocardiography at 3 months after irradiation; B. heart rate (bpm); C. R-wave amplitudes (mV); D. T-wave amplitudes (mV). Values are expressed as mean ± SD (n = 6 rabbits); ∗p < 0.05 and ∗∗∗P < 0.001 vs Control; #P < 0.05 and ##P < 0.01 vs RT.

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  Fig. 3. BMSCs inhibit radiation-induced oxidative stress and inflammation and improve functional heart parameters. The cTnI, BNP, SOD and TNF-α were measured after irradiation. A. cTnI; B. BNP; C. SOD; D. TNF-α. Values are expressed as mean ± SD (n = 6 rabbits); ∗∗∗P < 0.001 vs Control; #P < 0.05 and ###P < 0.001 vs RT.

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  Fig. 4. BMSCs reduce inflammation and myocardial fibrosis. Histopathology was performed on hematoxylin-eosin and Masson sections. A. HE sections and Masson sections; B. CVF: collagen volume fraction. C. Western blotting analysis of Collagen I and Collagen III in each group. D. Densitometric analysis of western blotting for Collagen I. E. Densitometric analysis of western blotting for Collagen III. Values are expressed as mean ± SD (n = 6 rabbits); Original magnification ×200; Scale bar = 100 μm ∗∗P < 0.01 and ∗∗∗P < 0.001 vs Control; ##P < 0.01 vs RT.

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  Fig. 5. BMSCs inhibit apoptosis. Apoptosis of cardiac tissue in each group. A. Representative images of apoptotic cells stained green with TUNEL in cardiac tissue. Total nuclei were stained blue with DAPI. B. Quantitative analysis of apoptotic rate. TUNEL-positive cells (%) are expressed as (number of apoptotic myocytes/total myocytes) ×100%. C. Western blotting analysis of cleaved caspase 3 in each group. D. Densitometric analysis of western blotting for cleaved caspase 3. Values are expressed as mean ± SD (n = 6 rabbits); Original magnification ×200; Scale bar = 100 μm ∗∗∗P < 0.001 vs Control; ##P < 0.01 and vs ###P < 0.001 vs RT.

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  Fig. 6. BMSCs reduce the expression of TGF-β1, Smad2/3 and p-Smad2/3. Immunohistochemical staining was performed to test the expression of TGF-β1. The level of TGF-β1, Smad2/3 and p-Smad2/3 was checked by Western blot. A: The expression and distribution of TGF-β1; B: IOD of TGF-β1 expression in the heart. C. Western blotting analysis of TGF-β1, Smad2/3 and p-Smad2/3 in each group. D. Densitometric analysis of western blotting for TGF-β1; E. Densitometric analysis of western blotting for Smad2/3 and p-Smad2/3. Values are expressed as mean ± SD (n = 6 rabbits); Original magnification ×200; Scale bar = 100 μm. IOD: integrated optical density. ∗∗P < 0.01 and ∗∗∗P < 0.001 vs Control; ##P < 0.01 vs RT.