bFGF、HGF与风湿性心脏病心房颤动患者心房纤维化的关系

来源 :中国临床研究 | 被引量 : 0次 | 上传用户:wangwang09
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目的研究碱性成纤维细胞生长因子(b FGF)、肝细胞生长因子(HGF)与风湿性心脏病心房颤动(房颤)患者心房纤维化的关系及其可能的分子机制。方法选取20例接受换瓣手术的风湿性心脏病患者,根据有无房颤分为房颤组10例和窦性心律(SR)组10例。在无菌条件下由手术者钳取小量的左心耳组织,制备石蜡切片并分别进行HE染色以及Masson染色;采用免疫组织化学技术测定左心耳心房肌组织中b FGF、HGF的蛋白表达,应用计算机图像分析系统,测定阳性染色面积密度并进行相对定量分析。蛋白印迹技术测定心房组织相关丝裂原活化蛋白激酶(MAPK)信号转导通路蛋白[c-Jun氨基末端激酶(JNK)、细胞外调节蛋白激酶(ERK)、p38]的相对表达量;最后将拍片所得图像输入自动图像分析仪以获取结果。结果 (1)两组间心肌细胞直径、心肌细胞间质纤维化面积比差异有统计学意义(P均<0.05);(2)房颤组b FGF在心房肌细胞间质内的分布明显多于SR组,两组间免疫组化b FGF面积密度差异有统计学意义(P<0.05),而HGF的分布明显少于SR组,两组间免疫组化HGF面积密度差异有统计学意义(P<0.05);(3)房颤组心房组织的JNK、ERK、p38蛋白的相对表达量高于SR组(P均<0.05)。结论风湿性心脏病房颤患者心肌组织中b FGF的表达增加及HGF的表达降低,可能激活了JNK、ERK、p38信号通路分子的磷酸化表达,从而促进心房纤维化,参与房颤的发生与维持。 Objective To investigate the relationship between bFGF, HGF and atrial fibrosis in atrial fibrillation patients with rheumatic heart disease and its possible molecular mechanisms. Methods Twenty patients with rheumatic heart disease undergoing valve replacement surgery were divided into 10 patients with atrial fibrillation group and 10 patients with sinus rhythm (SR) group according to the presence or absence of atrial fibrillation. Under aseptic conditions, a small amount of left atrial appendage was clamped by a surgeon to prepare paraffin sections and HE staining and Masson staining respectively. Protein expression of bFGF and HGF in atrial appendage of left atrial appendage was detected by immunohistochemistry. Computer image analysis system to determine the positive staining area density and relative quantitative analysis. Western blotting was used to determine the relative expression of atrial tissue-associated MAPK signal transduction pathway proteins (c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), p38) Filming the resulting image into an automated image analyzer for results. Results (1) There were significant differences in myocardial cell diameter and myocardial interstitial fibrosis between the two groups (all P <0.05). (2) The distribution of b FGF in atrial fibrillation group was significantly more in interstitial atrial myocytes In the SR group, there was significant difference in the area density of bFGF between the two groups (P <0.05), while the distribution of HGF in the SR group was less than that in the SR group. There was significant difference between the two groups in the area density of HGF P <0.05). (3) The relative expression of JNK, ERK and p38 in atrial fibrillation group was higher than that in SR group (all P <0.05). Conclusions The increased expression of b FGF and decreased expression of HGF in myocardium of patients with rheumatic heart disease may activate the phosphorylation of JNK, ERK and p38 signaling molecules, thereby promoting atrial fibrosis and atrial fibrillation maintain.
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