【摘要】 目的:探讨红花黄色素（SY）对糖尿病心肌病（DCM）大鼠心肌纤维化的影响及潜在机制。方法:采用高糖高脂饮食联合链脲佐菌素腹腔注射的方法复制DCM大鼠模型，设正常（Normal）组、模型（Model）组、SY组、转化生长因子-β₁（TGF-β₁）抑制剂SB431542组和SY+SB431542组，每组8只。SY组1次/d腹腔注射10mg/kg SY,SB431542组1次/d灌胃0.1mg/kg SB431542,SY+SB431542组1次/d腹腔注射10mg/kg SY+灌胃0.1mg/kg SB431542,Normal组和Model组1次/d腹腔注射生理盐水。治疗14d后，测定空腹血糖（FBG）水平，通过心脏超声检测心功能，酶联免疫吸附（ELISA）法测定血清乳酸脱氢酶（LDH）、心肌肌钙蛋白I（cTnI）、血管紧张素Ⅱ（AngⅡ）、基质裂解素2（ST2）水平，计算心脏指数（CI）,苏木素-伊红（HE）、马森（Masson）染色观察心肌组织病变和纤维化状况，蛋白免疫印迹（Western blot）法检测TGF-β₁、果蝇母源抗皮肤生长因子蛋白2/3（Smad2/3）、磷酸化Smad2/3（p-Smad2/3）、Smad7、胶原Ⅰ型和Ⅲ型（Collagen-Ⅰ、Collagen-Ⅲ）蛋白表达。结果:与Model组比较，SY组、SB431542组和SY+SB431542组大鼠FBG水平明显降低（P<0.05）;心功能明显改善[左心室射血分数（LVEF）和短轴缩短率（LVFS）明显升高，左心室收缩/舒张末期内径（LVIDs、LVIDd）明显降低（P<0.05）];血清LDH、cTnI、AngⅡ、ST2水平、CI均明显降低（P<0.05）;心肌纤维断裂，细胞空泡样变、坏死、数量减少，胞核深染等病变以及心肌纤维化状况均明显改善，胶原容积分数（CVF）明显降低（P<0.05）;心肌组织TGF-β₁、Collagen-I、Collagen-Ⅲ表达量及p-Smad2/3∕Smad2/3比值明显降低，Smad7表达量明显升高（P<0.05）。SY+SB431542组对各检测指标的影响均明显优于SY组和SB431542组（P<0.05）。结论:SY具有抑制DCM大鼠心肌纤维化的作用，可能与下调TGF-β₁/Smads通路，减轻细胞外基质沉积（ECM）有关。更多还原

【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.更多还原