Objective To investigate the effect of sinapic acid (SA) on myocardial fibrosis in type 2 diabetic mice and its related mechanism. Methods Forty C57BL/6J mice were divided into the normal group (NOR), the type 2 diabetes model group (DM), the metformin group (DM+MET, 200 mg/kg), the low-dose sinapic acid group (DM+SAL, 20 mg/kg), and the high-dose sinapic acid group (DM+SAH, 60 mg/kg). The type 2 diabetes model was induced with a high-fat diet (HFD) in combination with the injection of streptozotocin (STZ, 35 mg/kg). The intervention lasted four weeks. All animals were sacrificed and the cardiac index was calculated. Myocardial pathological changes and histological fibrosis levels were evaluated through HE and Masson's staining. The commercial kits were used to assess oxidative stress indicators, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), in addition to serum cholesterol (TC) and triglycerides (TG), and inflammation indicators such as interleukin-1β (IL-1β), IL-6, IL-18, and tumor necrosis factor-α (TNF-α). Immunohistochemistry was used to measure the levels of cardiac α-SMA, while Western-blot was employed to detect the levels of TGF-β1, α-SMA, Smad4, and Smad7 in the cardiac tissues. Results In comparison to the NOR group, the DM group exhibited disorganized myocardial morphology, increased cardiac index (P<0.05), augmented myocardial fibrosis level (P<0.05), elevated levels of serum MDA, TG, TC, IL-β1, IL-6, IL-18, and TNF-α (P<0.05), and up-regulated expressions of myocardial TGF-β1, α-SMA, and Smad4 (P<0.05). Conversely, there were significantly decreased levels of serum SOD, CAT, GSH-Px, and myocardial expression of Smad7 (P<0.05). Compared to the DM group, the cardiac index of mice in the DM+MET, DM+SAL and DM+SAH groups was significantly lower (P<0.05), myocardial fibrosis was reduced (P<0.05), serum levels of MDA, TG, TC, IL-1β, IL-6, IL-18, and TNF-α were significantly decreased (P<0.05), and TGF-β1, α-SMA, and Smad4 protein expressions were significantly reduced (P<0.05). Meanwhile, serum levels of SOD, CAT, GSH-Px, and myocardial Smad7 expression were significantly increased (P<0.05). Conclusion Sinapic acid alleviates myocardial fibrosis in T2DM mice, which is related to the regulation of the TGF-β/Smads signaling pathway.
Key words
sinapic acid /
type 2 diabetes /
myocardial fibrosis /
mice
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