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-β_(1)(TGF-β_(1))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-β_(1)、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-β_(1)、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-β_(1)/Smads通路,减轻细胞外基质沉积(ECM)有关。
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-β_(1)(TGF-β_(1))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-β_(1),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-β_(1),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-β_(1)/Smads pathway and alleviating extracellular matrix(ECM)deposition.
出处
《河北医学》
2025年第1期40-46,共7页
Hebei Medicine
基金
河北省医学科学研究课题计划,(编号:20191844)。
