摘要
目的 探讨藏红花素对心肌梗死后心力衰竭(心衰)大鼠心功能和心肌纤维化的影响及可能机制.方法 采用结扎左冠状动脉(冠脉)前降支的方法构建心肌梗死后心衰大鼠模型,取80只成模大鼠随机分为模型组、卡托普利(10 mg/kg)组和藏红花素低剂量组(20 mg/kg)、中剂量组(40 mg/kg)、高剂量组(80 mg/kg),每组各16只;另取16只大鼠设为假手术组.造模完成后,各组分别灌胃给药,1/d.4周后,通过超声影像检测心功能指标[左室射血分数(LVEF)、左室短轴缩短分数(LVFS)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)],ELISA法检测血清心肌肌钙蛋白T(cTnT)、血管紧张素Ⅱ(AngⅡ)、脑钠肽(BNP)、醛固酮(ALD)含量,TTC染色法计算心肌梗死面积,计算左室心肌肥厚指数(LVHI),Masson染色观察心肌组织纤维化状况,ELISA法检测心肌组织白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)含量,Western blot法检测Toll样受体4(TLR4)、核因子-κB p65(NF-κB p65)、转化生长因子-β1(TGF-β1)、Ⅰ型胶原(Collagen-Ⅰ)、Collagen-Ⅲ蛋白表达.结果 与模型组比较,卡托普利组和藏红花素中、高剂量组大鼠LVEF和LVFS明显升高,LVEDD和LVESD明显降低(P＜0.05);血清cTnT、AngⅡ、BNP、ALD含量和心肌梗死面积、LVHI明显降低(P＜0.05);心肌组织纤维化状况明显改善,胶原容积分数(CVF)明显降低(P＜0.05);心肌组织IL-1β、IL-8、TNF-α含量和TLR4、NF-κB p65、TGF-β1、Collagen-Ⅰ、Collagen-Ⅲ表达量均明显降低(P＜0.05).藏红花素上述作用呈一定剂量依赖性.除LVHI、IL-8外,藏红花素高剂量组对其它指标的作用明显优于卡托普利组(P＜0.05).结论 藏红花素具有抑制心肌梗死后心衰大鼠心肌纤维化、改善心功能的作用,可能与抑制TLR4/NF-κB信号通路,抑制炎症反应和细胞外基质生成有关.
Abstract
Objective To investigate Crocin's effect and possible mechanism on cardiac function and myocardial fibrosis in rats with heart failure after myocardial infarction.Methods The rat model with heart failure after myocardial infarction was established by ligation of the anterior descending branch of the left coronary artery.Eighty model rats were randomly divided into the model group,Captopril(10 mg/kg)group,Crocin low,medium,and high dose(20,40,80 mg/kg)groups,with 16 rats in each group;another 16 rats were selected as sham operation group.After modeling,the rats in each group were given intragastric administration,once a day.Four weeks later,the cardiac function indexes[left ventricular ejection fraction(LVEF),left ventricular short axis shortening fraction(LVFS),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)]were detected by ultrasound imaging;the levels of cardiac troponin T(cTnT),angiotensin Ⅱ(Ang Ⅱ),brain natriuretic peptide(BNP)and aldosterone(ALD)in serum were determined by ELISA;the myocardial infarction size was calculated by TTC staining;the left ventricular myocardial hypertrophy index(LVHI)was calculated;the myocardial fibrosis was observed by Masson staining;the contents of interleukin-1β(IL-1β),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)in myocardial tissue were determined by ELISA;the expressions of Toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),transforming growth factor-β1(TGF-β1),Collagen Ⅰand Collagen Ⅲ were detected by Western blot.Results Compared with the model group,the LVEF,LVFS were significantly increased in the Captopril group and Crocin medium and high dose groups,while the LVEDD,LVESD were significantly decreased(P＜0.05).The levels of cTnT,Ang Ⅱ,BNP,ALD in serum and the myocardial infarction area,LVHI were significantly decreased(P＜0.05).The myocardial fibrosis was significantly improved,and the collagen volume fraction(CVF)was significantly decreased(P＜0.05).The contents of IL-1β,IL-8,TNF-α and the expressions of TLR4,NF-κB p65,TGF-β1,Collagen I,and Collagen Ⅲ in myocardial tissue were significantly decreased(P＜0.05).The above effects of Crocin were dose-dependent.Except for LVHI and IL-8,the impact of the Crocin high-dose group on other indexes were significantly better than those in the Captopril group(P＜0.05).Conclusion Crocin can inhibit myocardial fibrosis and improve cardiac function in rats with heart failure after myocardial infarction,which may be related to the inhibition of TLR4/NF-κB signaling pathway,inflammation and extracellular matrix generation.
NETL
NSTL
维普
万方数据