摘要
目的:采用扩散张量成像(DTI)检测心肌梗死后梗死区、边缘区及非梗死区的微观结构重构,并结合血清中血管紧张素-Ⅱ(Ang-Ⅱ)和转化生长因子-β1(TGF-β1)的表达水平,探索心肌梗死后心室重构的机制以及两者的内在联系。方法2015年8至12月,选用34只成年雄性兔,分为正常组(n=5),假手术组(n=5)以及心肌梗死术后1、2、4周组各8只。通过结扎冠状动脉左室支,建立兔心肌梗死模型,术后死亡3只(术后1、2、4周各1只),存活31只。所有存活兔在相应时间点处死获取离体心脏标本,在处死前于耳缘静脉采血,获取血清,采用ELISA法检测血清中Ang-Ⅱ及TGF-β1含量,离体心脏标本行3.0 T MR-DTI扫描,测量梗死区、边缘区和非梗死区的各向异性分数(FA)值和平均扩散系数(MD)值。在心肌梗死不同时间点各测量指标比较采用单因素方差分析,DTI指标与血清标志物之间的相关性分析采用Pearson相关。结果梗死区和边缘区的FA值术后1周显著下降,分别为0.185±0.012和0.221±0.005,之后下降较缓慢,均在第4周时达最低,分别为0.138±0.012和0.201±0.014,与正常组比较差异均有统计学意义(F值分别为229.130、38.321,P〈0.01)。梗死区MD值在术后呈迅速、显著升高趋势,术后1、2、4周MD值分别为(0.869±0.085)×10-3、(0.955±0.109)×10-3、(1.113±0.100)×10-3mm2/s,边缘区MD值呈缓慢、渐进性升高,MD值分别为(0.809±0.111)×10-3、(0.830±0.043)×10-3、(0.912±0.100)×10-3mm2/s,两者均在第4周时达高峰,与正常组比较差异有统计学意义(F值分别为20.756、6.448,P〈0.01)。Ang-Ⅱ和TGF-β1变化相似,均是在术后第1周内迅速、显著上升达高峰,在第2周小幅下降,随后基本稳定。梗死区和边缘区的FA值和血清中Ang-Ⅱ(r值分别为-0.681、-0.729,P〈0.01)、TGF-β1(r值分别为-0.555、-0.608,P〈0.01)均呈显著负相关。结论心肌梗死后心室重构复杂且动态变化,尤其是在梗后1周内,梗死区和边缘区组织重构最为迅速且明显,相关调控因子也同时达高峰,Ang-Ⅱ及TGF-β1对心室重构起调控作用。
Objective To gain insight into myocardial microstructure remodeling in the core-infarction zone (CIZ), peri-infarction zone(PIZ) and non-infarction zone (NIZ) using diffusion tensor imaging(DTI), and combined with angiotensin-Ⅱ(Ang-Ⅱ) and transforming growth factor-β1(TGF-β1) in the serum, so as to explore the ventricular remodeling(VR) mechanism at both the microstructural level and molecular level and correlations between both. Methods From August to December 2015, we chose 34 adult male rabbits which were divided into normal group(n=5), sham-operation group(n=5), and MI group with 8 rabbits at 1, 2 and 4 w respectively. Thirty-one survived and 3 died, with one at the 1, 2 and 4 w respectively. The MI model was established by ligating the left ventricular branch of the coronary artery. A serum sample was collected from the ear vein of each rabbit prior to execution. Ang-Ⅱand TGF-β1 of each sample were measured using the ELISA method. Each rabbit was executed to obtain the whole heart for ex-vivo 3.0 T DTI. Fractional anisotropy(FA) and mean diffusion(MD) coefficient values were measured in the CIZ, PIZ and NIZ. Comparison of DTI indicators (FA and MD values) and serum biomarkers (Ang-Ⅱand TGF-β1) between the normal group and the sham-operation group were made with independent sample t-test, while comparison among MI subgroups at the different time points and two control groups were analyzed using one-way ANOVA. The Pearson correlation analysis was done between DTI indicators and serum biomarkers. Results Both the FA values of the CIZ and PIZ significantly decreased in the 1st week, 0.185±0.012 and 0.221±0.005 respectively, then decreased slowly, both reached the lowest values at the 4th week, 0.138 ± 0.012 and 0.201 ± 0.014 respectively. The FA values at 1, 2 and 4 w in the CIZ and PIZ were statistically significant compared with the normal group(F=229.130, 38.321,P〈0.01), respectively. The MD values in the CIZ increased rapidly and dramatically in four weeks after operation, (0.869 ± 0.085) × 10-3, (0.955 ± 0.109) × 10-3, (1.113 ± 0.100) × 10-3mm2/s respectively. While those in the PIZ increased slowly and gradually, (0.809 ± 0.111) × 10-3, (0.830 ± 0.043) × 10-3, (0.912 ± 0.100) × 10-3mm2/s respectively. Both were reaching the peak at the 4th week synchronously. The MD values at 1, 2 and 4 w in the CIZ and PIZ were statistically significant compared with the normal group(F=20.756、6.448,P〈0.01). The Ang-II and TGF-β1 changed similarly, both increased rapidly and significantly during the 1st week, which appeared a small reduction at the 2nd week. Then, they stayed stable. In the CIZ and PIZ, the FA had negative correlations with Ang-Ⅱand TGF-β1, with rCIZ=-0.681 and rPIZ=-0.729 (FA vs. Ang-Ⅱ) and rCIZ=-0.555 and rPIZ=-0.608 (FA vs. TGF-β1). Conclusions The ventricular remodeling after MI was a complex and dynamic process, especially in the 1st week, the CIZ and PIZ remodeled very quickly and obviously, and the Ang-Ⅱ and TGF-β1 reached the peak meanwhile, validating they mediated in regulating VR.
作者
喻思思
殷亮
李淑豪
邹倩
周丽
杨震
龚良庚
Yu Sisi Yin Liang Li Shuhao Zou Qian Zhou Li Yang Zhen Gong Lianggeng(Department of MRI, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Chin)
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2016年第12期968-973,共6页
Chinese Journal of Radiology
基金
基金项目:国家自然科学基金(81360216,81660284)
江西省自然科学基金(20142BAB205061,20161ACB20013)
江西省科技计划重点项目(20121BBG70040)
关键词
心室重构
心肌梗塞
磁共振成像
血管紧张素Ⅱ
Ventricular remodeling
Myocardial infarction
Magnetic resonance imaging
AngiotensinⅡ