FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model

Figure 1. FTZ ameliorated the changes in blood glucose, serum insulin, and body weight in diabetic mice. Mice were treated with streptozotocin (STZ) (50 mg/kg/d, injected intraperitoneally every day for 5 consecutive days) followed by treatment with or without FTZ (3 g/kg/d, administrated intragastrically every day for one month). At the end of the experiment, blood glucose (a), body weight (b), and serum insulin (c) were tested. n = 5. ∗p < 0.05, ∗∗p < 0.011, and ∗∗∗p < 0.001.

Figure 2. FTZ improved the cardiac function in diabetic mice. (a) The early to late diastolic peak velocity (E/A) ratio was detected by Doppler echocardiography. (b) The ventricular wall thickness was detected by M-mode echocardiography. (c) H&E staining. Bar = 50 μm. n = 5. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.

Figure 3. FTZ inhibited the inflammation in diabetic mice. (a) Serum levels of IL-12, IL-6, TNF-α, IL-1β, CCL2, and IL-10 were measured by ELISA. (b) The myocardial mRNA levels of IL-12, IL-6, Tnf-α, IL-1β, Ccl2, and Ccr2 were tested by Q-PCR. n = 5. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.

Figure 4. FTZ alleviated diabetes-induced cardiac fibrosis. (a) Histopathological features of collagen deposition by Sirius Red staining of heart sections from mice model and quantification of Sirius Red staining. Bar = 100 μm. (b) The myocardial mRNA expressions of Col1al, Col3al, α-sma, Acta2, and Tgf-β1 were tested by Q-PCR. n = 5. (c) The protein expressions of Col3a1, MMP2, and MMP9 in hearts were tested by Western blot. n = 3. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.

Figure 5. FTZ decreased diabetes-induced cardiac apoptosis. (a) TUNEL staining and quantification. Bar = 50 μm. n = 5. (b) The protein expressions of cleaved-Caspase-3 in hearts were tested by Western blot. n = 3. ∗p < 0.05 and ∗∗p < 0.01.

Figure 6. Component-target-pathway network of FTZ formula in the treatment of DCM. Nodes in red are considered as important, and the green nodes are considered as less important.

Figure 7. Effects of FTZ on the activity of AKT, ERK, and STAT3 in hearts of DCM. The proteins of p-AKT, AKT, p-ERK, ERK, p-STAT3, and STAT3 in hearts were tested by Western blot. n = 3. ∗p < 0.05 and ∗∗p < 0.01.

Figure 8. FTZ inhibited the expressions of fibrotic factors in C3H/10T1/2 cells. C3H/10T1/2 cells were treated with TGF-β1 (50 ng/ml) and different FTZ (1 μg/ml, 10 μg/ml, and 100 μg/ml) for 12 h or 24 h. (a) The mRNA levels of Col1al, Col3al, and Acta2 in cells were tested by Q-PCR. (b) The protein changes of α-SMA, CTGF, p-AKT, AKT, p-ERK, ERK, p-STAT3, and STAT3 in cells were tested by Western blot. n = 3. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.