摘要
目的探讨心房颤动的发生过程中是否存在心房肌的纤维化，以及TGF-β1／TAK1信号系统在心房颤动心肌纤维化中的作用。方法20只新西兰大白兔随机分成两组：假手术组（GroupS）和快速起搏组（GroupP）。给予兔左心房心外膜电起搏，以900次／min高频起搏，建立房颤模型。起搏前后及房颤后记录心电图。取兔心房组织，观察细胞结构变化（HE染色），比较左房重量指数及胶原蛋白的表达水平（Masson染色），免疫组化、Westen—blot检测TGF-61、TAK1蛋白表达水平，PCR检测TGF-β1mRNA、TAKImRNA的表达水平。结果①起搏兔的左房重量、左房重量指数明显高于GroupS。Masson染色显示起搏兔的左心房心肌间质胶原显著增多。②起搏组的TGF—β1、TAK1的表达明显高于GroupS。③在起搏组中，代表心肌纤维化的心肌间质胶原及LAWI与TGF-β1、TAK1的表达密切相关（P〈0．05），其中与TGF—β1呈正相关（R2=0．72，P〈0．05），与TAKI亦呈正相关（R^2=0．762，P〈0．05）。结论心房颤动在发生早期即存在心房组织的纤维化。快速起搏诱导的心房颤动早期，TGF-β1／TAK1通路信号mRNA及蛋白表达水平明显升高，TGF-β1／TAK1通路信号可能是心房纤维化信号途径之一，可能成为房颤治疗的新靶点。
Objective To study the existence of atrial fibrosis occurring during the early course of atrial fibrillation and the effect of TGF-β1/TAKI signal system on myocardial fibrosis during atrial fibrillation. Methods 20 male rabbits were randomly and equally divided into 2 groups： Group S （sham operation, no pacing） and Group P （left atrium pacing, 900 bpm）. Pacing and recording electrodes were sutured to the left atrium. After a 7-day recovery period, rapid pacing at 900 ppm was initiated. Electrocardiogram（ECG） was monitored and recorded before operation and during pacing. At the end of the experiment, the atrial tissue samples were collected for molecular biological test and the changes of tissue were studied by HE staining. Comparison of left atrial mass index and the content of collagen were examined by Masson three-color staining. The mRNA expression and protein expression of TGF-β1 and TAK1 were determined by PCR and western-blotting. Results were presented as means＋SD. Differences among the groups were compared by one-way ANOVA, followed by Student-Newmantests. Correlation analysis was assessed using Pearson＇s correlation P〈0.05 was considered significant. Results （1） Pacing rabbits showed atrial fibrosis reflected by left atrial mass （LAM）, left atrial mass index （LAMI） and increased collagen deposition in Masson three-color staining compared with group S. （2）The protein and mRNA expression level of TGF-β1/TAK1 was increased in the left atrium of pacing rabbits compared with Group S with significant difference. （3）Significant positive correlation between myocardial fibrosis and TGF-β1 expression （R^2= 0.72, P〈0.05） and TAK1 expression （R2=0.762, P〈0.05）. Conclusion The atrial fibrosis is present in the early term of atria fibrillation. The mRNA and protein expression level of TGF-β1/TAK1 signal pathway are significantly elevated during the early term of rapid pacing-induced atrial fibrillation. TGF- β1/TAK1 signal pathway may be an important way in atrial fibrosis process, which may become the new target for atrial fibrillation treatment.
出处
《中国心血管病研究》
CAS
2012年第12期932-936,960,共6页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金项目（项目编号：39700059）
辽宁省自然科学基金项目（项目编号：20092114）
沈阳市科学技术项目（项目编号：F11-264-1-75）
