张丽娜,刘津军,王绍伟
ZHANG Lina,LIU Jinjun,WANG Shaowei

• 1:邯郸市中心医院心内三科

摘要(Abstract)：

目的探讨大蒜素对急性心肌梗死(AMI)大鼠心功能和心肌纤维化的影响及机制。方法将100只SD大鼠随机均分为假手术组、模型组和大蒜素低、中、高剂量(5、10、20 mg/kg)组,后4组大鼠麻醉开胸后结扎左冠状动脉前降支复制AMI大鼠模型,假手术组大鼠仅做手术不结扎血管,大蒜素各组大鼠分别腹腔注射2.5、5、10 g/L的大蒜素溶液2 m L/kg),假手术组和模型组注射同剂量生理盐水; 24 h后,应用动物超声仪检测左心室舒张内径(LVIDd)、收缩末期内径(LVIDs),射血分数(EF),每搏输出量(SV)],ELISA法检测血清NT-proBNP水平,计算心脏指数,HE染色法行心肌组织学观察,Masson染色法观察心肌纤维化并计算心肌间质胶原容积分数(CVF),Western blot法测定心肌胶原蛋白Ⅰ(CollagenⅠ)、CollagenⅢ、基质金属蛋白酶-2(MMP-2)、转化生长因子-β(TGF-β)以及磷酸化Smad 2(p-Smad2)蛋白的表达。结果与模型组比较,大蒜素中、高剂量组大鼠LVIDd及LVIDs降低、EF及SV升高(P <0.05或P <0.01)、血清NT-proBNP水平及心脏指数降低(P <0.01),心肌细胞形态结构病变和心肌纤维化程度明显改善,CVF明显降低(P <0.05或P <0.01),CollagenⅠ、CollagenⅢ、MMP-2、TGF-β以及p-Smad2蛋白表达下调(P <0.01)。结论大蒜素具有保护AMI大鼠心功能并抑制心肌纤维化的作用,其机制可能与抑制TGF-β/Smad信号通路、下调CollagenⅠ、CollagenⅢ、MMP-2蛋白表达有关。
Objective To investigate the effect and mechanism of Allicin on cardiac function and myocardial fibrosis in rats with acute myocardial infarction( AMI). Methods 100 SD rats were randomly divided into sham group,model group and allicin low-,medium-,high dose( 5,10,20 mg/kg,respectively) groups,20 rats/group. After the rats were anesthetized and given thoracotomy,the left anterior descending( LAD) coronary artery was ligated to establish AMI model in model and allicin groups but not in sham group. At 10 min before the surgery,allicin low-,medium-and high-dose groups were intraperitoneally injected with 2. 5,5,and 10 g/L of allicin solution( the injection volume: 2 m L/kg). Sham and model groups were given 0. 9% sodium chloride solution. At 24 h after the surgery,left ventricular diastolic inner diameter( LVIDd),end-systolic diameter( LVIDs),ejection fraction( EF) and stroke volume( SV) were detected by animal ultrasonic instrument. The level of NT-proBNP in serum was detected by ELISA assay. The cardiac index was calculated. The myocardial pathological changes and fibrosis degree were observed using HE staining. Masson staining was used to monitor and calculate myocardial interstitial collagen volume fraction( CVF). The protein expression levels of Collagen Ⅰ,Collagen Ⅲ,MMP-2,TGF-β,and phospho-Smad2 were detected in myocardial tissue by Western blot. Results Compared with model group,allicin medium-and highdose groups had reduced levels of the LVIDd and LVIDs( P < 0. 05),increased levels of EF and SV( P < 0. 01), decreased levels of NT-proBNP and cardiac indexes( P < 0. 01), improved morphological and structural changes of myocardial cells and decreased CVF( P < 0. 01) as well as attenuated myocardial fibrosis. Additionally,the expression levels of Collagen Ⅰ,Collagen Ⅲ,MMP-2,TGF-β, and phospho-Smad2 were significantly downregulated( P < 0. 05 or P < 0. 01).Conclusions Allicin can protect the cardiac function and inhibit myocardial fibrosis of AMI rats. Its mechanism may be related to inhibiting TGF-β/Smad signaling pathway and down-regulating the expression of Collagen Ⅰ,Collagen Ⅲ,and MMP-2 proteins.

关键词(KeyWords)： 大鼠;急性心肌梗死;心脏功能;心肌纤维化;胶原蛋白;TGF-β/Smad信号通路;大蒜素
rats;acute myocardial infarction(AMI);cardiac function;myocardial fibrosis;collagen;TGF-β/Smad signaling pathway;allicin

Abstract:

Keywords:

基金项目(Foundation): 河北省医学科学研究课题计划(20191836)

作者(Author): 张丽娜,刘津军,王绍伟
ZHANG Lina,LIU Jinjun,WANG Shaowei

DOI: 10.19367/j.cnki.2096-8388.2021.01.007

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