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作 者:刘英[1] 廖玉华[1] 程翔[1] 李彬[1] 葛洪霞[1] 张玲[1] 郭张强[1]
机构地区:[1]华中科技大学同济医学院心血管病研究所,协和医院心内科,湖北武汉430022
出 处:《中国病理生理杂志》2005年第12期2305-2309,共5页Chinese Journal of Pathophysiology
基 金:SUPPORTED BY THE FOUNDATION NF THE NATIONAL NATURAL SCIENCE FOUNDATION OF CHINA(NO.30370574)
摘 要:目的:探讨大鼠急性心肌梗死(AMI)后心肌纤维化和TGF-Β1表达及炎症反应的分子机制。方法: 建立大鼠AMI模型及假手术组,于术后第1、4和8周末测血流动力学后取心脏。RT-PCR和免疫组化SABC法检测 FGF-Β1岛基因和蛋白的表达。用氯胺T法测心肌组织羟脯氨酸的含量。心肌病检观察心肌组织炎症细胞浸润情况。结果:与假手术组相比,AMI后第1、4和8周末血流动力学有明显改变(P<0.01)。在梗死区、交界区和非梗死区羟脯氨酸和TGF-Β1基因和蛋白表达均增高(P<0.05),第1周的表达高于第4和8周。羟脯氨酸和TGF-Β1蛋白表达呈现明显正相关(R=0.75-0.99,P<0.05)。AMI后第1周梗死区和交界区炎症细胞浸润明显,第4和8周心肌炎症细胞减少。TGF-Β1在梗死后1’周时主要见于心肌细胞、中性粒细胞、巨噬细胞和部分淋巴细胞的胞浆内表达,在4 周和8周见于成纤维母细胞及间质。结论:AMI后心肌细胞、炎症细胞、成纤维母细胞胞浆及基质中TGF-Β1表达增高,与羟脯氨酸的变化及炎症过程存在联系,可能在AMI后心室重塑和心肌炎性修复过程中起重要作用。AIM: To explore the molecular mechanisms about fibrosis and transforming growth factor (TGF) - β1 as well as inflammation in rats heart 'after acute myocardial infarction (AMI). METHODS: AMI model in rats was produced by left coronary 'artery ligation. Samples of rat cardiac tissue were collected at the end of 1 week, 4 weeks and 8 weeks. Hemodynamics had been performed before rats were sacrificed. Reverse transcription polymerase chain reaction (RT- PCR) and immunohistochemical methods were used to analyze mRNA expression and protein production of TGF- β1, respectively. Hydroxypmline was determined by chloramines T method. HE staining was resorted to analyze pathological myocardium after AMI. RESULTS: There were remarkable differences in hemodynamics between AMI groups and sham group ( P 〈 0.01 ). Compared with sham group, TGF- β1 mRNA expression and protein production and hydroxypmline quantification were enhanced greatly. Among them, the levels of TGF - β1 and hydroxypmline at 1 week were higher than those at 4 weeks or 8 weeks. A positive correlation between TGF- β1 protein and hydroxypmline was presented ( r = 0.75 - 0.99, P 〈 0.05). In microscope, leucocytes infiltrated significantly in the infarcted and border myocardium at 1 week after AMI, and were rarely seen at 4 weeks and 8 weeks. TGF - β1 protein were detected in cytoplasm of cardiac myocyte and leucocytes at 1 week, and at 4 and 8 weeks in myofibroblast and interstitial. CONCLUSIONS: TGF- β1 is upregulated and found in cytoplasm of cardiac myocyte and leucocytes as well as myofibroblast in heart after AMI, which is associated with dynamic changes of hydroxypmline content and inflammation. TGF - β1 is showed to play an important role in myocardial inflammatory repair and ventricular remodeling after AMI.
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