bFGF、HGF与风湿性心脏病心房颤动患者心房纤维化的关系

Relationship of b FGF,HGF and atrial fibrosis in rheumatic heart disease patients with atrial fibrillation

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 study the associations of basic fibroblast growth factor（ b FGF） and hepatocyte growth factor（ HGF） with atrial fibrosis in rheumatic heart disease patients with atrial fibrillation（ AF）,and reseach the potential molecular mechanism. Methods Twenty patients with rheumatic heart disease who received valve replacement operation were selected and divided into two groups（ n = 10 each） ： AF group and sinus rhythm group（ SR group） according to whether there was AF. A small amount of left auricle tissues were taken with the pliers by operator under sterile condition,and the paraffin sections were prepared for HE staining and Masson staining. Immunohistochemistry was used to detect the expressions of b FGF and HGF proteins in the atrial myocardium tissues of left auricle. The computer image analysis system was used to detect the density of their positive staining area and make relative quantitative analysis. Western blot method was used to detect the relative expression qualities of atrial tissues-related MAPK signal transduction pathway proteins JNK（ Jun N-terminal kinase）,ERK（ extracellular signal-regulated kinase） and p38. Results There were statistical differences in myocardial cell diameter and interstitial fibrosis area ratio between two groups（ all P〈0. 05）. The distribution of b FGF in the stroma of atrial muscle cells in AF group was significantly more than that in SR group,and there was significant difference in the density of its positive staining area between two groups（ P〈0. 05）. The distribution of HGF in the stroma of atrial muscle cells in AF group was significantly less than that in SR group,and there was significant difference in the density of its positive staining area between two groups（ P〈0. 05）. The relative expression qualities of JNK,ERK and p38 in AF group were significantly higher than those in SR group（ all P〈0. 05）. Conclusions The increase of b FGF expression and the decrease of of HGF expression in cardiac tissue of rheumatic heart disease patients with AF may activate the phosphorylation expressions of JNK,ERK and p38 signaling pathway molecules,and thus promote atrial fibrosis and participate in the occurrence and maintenance of atrial fibrillation.