红花黄色素调节TGF-β<sub>1</sub>/Smads通路对糖尿病心肌病大鼠心肌纤维化的影响

doi:10.3969/j.issn.1006-6233.2025.01.007

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Abstract Objective: To investigate the effect of safflower yellow (SY) on myocardial fibrosis in diabetic cardiomyopathy (DCM) rats and its potential mechanism. Methods: The DCM rat model was prepared by a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin and divided into five groups: Normal, Model, SY, transforming growth factor-β₁ (TGF-β₁) inhibitor SB431542, and SY+SB431542, with eight rats in each group. The SY group received 10 mg/kg SY via intraperitoneal injection once daily, the SB431542 group received 0.1 mg/kg SB431542 via intragastric administration once daily, and the SY+SB431542 group received both 10 mg/kg SY via intraperitoneal injection and 0.1 mg/kg SB431542 via intragastric administration once daily. The Normal and Model groups received normal saline via intraperitoneal injection once daily. After 14 days of treatment, fasting blood glucose (FBG) levels were measured; cardiac function was assessed using echocardiography; serum levels of lactate dehydrogenase (LDH), cardiac troponin I (cTnI), angiotensin II (Ang II), and soluble ST2 (sST2) were determined by enzyme-linked immunosorbent assay (ELISA); and cardiac index (CI) was calculated. Myocardial tissue lesions and fibrosis were observed using hematoxylin-eosin (HE) staining or Masson staining, and the expression of TGF-β₁, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3), Smad7, Collagen-I, and Collagen-III was detected by Western blot. Results: Compared with the Model group, cardiac function [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly increased, while left ventricular end-systolic diameter (LVIDs) and end-diastolic diameter (LVIDd) were significantly decreased (P<0.05)] was significantly improved in the SY, SB431542, and SY+SB431542 groups. FBG levels and serum levels of LDH, cTnI, Ang II, sST2, and CI were significantly decreased (P<0.05). Myocardial histopathological changes such as myofiber rupture, cellular vacuolation, necrosis, decreased cell number, nuclear hyperstaining, and myocardial fibrosis were significantly improved, and collagen volume fraction (CVF) was significantly decreased (P<0.05). Expression of TGF-β₁, Collagen-I, Collagen-III, and the p-Smad2/3:Smad2/3 ratio in myocardial tissue was significantly decreased, while Smad7 expression was significantly increased (P<0.05). The effects of the SY+SB431542 group on the detection indices were significantly better than those of the SY and SB431542 groups (P<0.05). Conclusion: SY can inhibit myocardial fibrosis in DCM rats, which may be related to downregulating the TGF-β₁/Smads pathway and alleviating extracellular matrix (ECM) deposition.

Key words： Diabetic cardiomyopathy Safflower yellow Myocardial fibrosis TGF-β₁/Smads pathway

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.01.007 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I1/40

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