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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
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)
关键词
心肌梗死
心室复建
炎症
羟脯氨酸
转化生长因子Β
Myocardial infarction
Ventricular remodeling
Inflammation
Hydroxyproline
Transforming growth factor beta