简介:在成人和儿童的某些临床疾病中,可能会发生右心室重构并随后出现功能损害。触发因素,分子机制,and,尤其是,随着时间的推移,演变仍然不为人所知。与右心室(RV)重塑相关的左心室(LV)变化也知之甚少。目的:本研究旨在评估RV的形态学,功能,与对照组大鼠相比,接受肺动脉束带的大鼠的基因表达参数,随着这些参数的时间演变,并分析大鼠及其对照组随时间的肺动脉束带对RV重塑的影响,组织学,基因表达,和功能性能。方法:健康6周龄雄性Wistar-EPM大鼠,体重170-200g。超声心动图检查后的一天,根据是否进行肺动脉束带(PAB)手术的动物(对照组),然后根据随访时间将他们随机分为亚组:72小时,或2、4、6或8周。在每个子组中,进行了以下检查:新的超声心动图,血液动力学研究,用于形态学分析(肥大和纤维化)的材料的收集,和分子生物学(基因表达)。结果表示为平均值±平均值的标准偏差。双向方差分析和Tukey后检验比较了亚组的变量和进化随访时间。采用的显著性水平为5%。结果:各亚组之间的肺和肝中水的百分比没有显着差异(肺中水的百分比为76%至78%,肝的百分比为67%至71%)。在所有亚组的PAB动物中,右室的重量均显着较高(RVPAB的重量为0.34至0.48g,和控制主体,从0.17到0.20g;右心房(RA)的PAB从0.09到0.14g;对照组从0.02到0.03g)。在PAB动物的RV中,与对照组(34.2μm3-57.2μm3)相比,肌细胞核体积(97μm3-183.6μm3)显着增加,在PAB随访时间较短的亚组中更为强烈,和纤维化百分比(5.9%-10.4%vs.0.96%-1.18%)随着PAB随访时间的延长而升高。在超声心动图结果中,所有PAB组的心肌厚度均显着增加(与对照组相比,0.09-0.11cm-0.04-0.05cm),但右心室舒张内径没有变化。从PAB的2到8周,S波(S')(0.031cm/s和0.040cm/s),和分数面积变化(FAC)(51%-56%),RV收缩功能参数显着低于各自的对照组(0.040cm/s至0.050cm/s和61%-67%)。此外,在RV中观察到与肥大和细胞外基质相关的基因在初始亚组中的较高表达以及在较长的随访PAB亚组中的凋亡基因。另一方面,LV重量在有和没有PAB的动物之间没有差异。PAB动物的细胞核体积大于对照组(74μm3-136μm3;40.8μm3-46.9μm3),4周和8周PAB组(1.2%和2.2%)的纤维化百分比显着高于对照组(0.4%和0.7%)。超声心动图显示,PAB动物和对照组之间的舒张直径和LV心肌厚度没有差异。在所有亚组中,PAB动物和对照组之间,超声心动图的等容弛豫时间和E波减速时间的测量值不同。但在血流动力学研究中,舒张功能没有变化。与各种功能相关的基因表达也增加,特别是肥大。结论:1)接受肺动脉束带的大鼠表现出与肥大相适应的RV重塑。这种改变是由基因表达增加和功能改变介导的,这与纤维化的发作相吻合。2)RV的结构变化,比如体重,心肌厚度,肌细胞核体积,和纤维化程度,根据暴露于肺动脉带的时间进行修改,并与基因表达的变化有关,强调从早期到晚期随访时间从α到β模式的变化。3)研究表明,左心室发生了组织学改变,伴随着基因表达的改变,同时在右心室中发现了改变。
Introduction: Right ventricular
remodeling with subsequent functional impairment can occur in some clinical conditions in adults and children. The triggering factors, molecular mechanisms, and, especially, the evolution over time are still not well known. Left ventricular (LV) changes associated with right ventricular (RV)
remodeling are also poorly understood. Objectives: The
study aimed to evaluate RV morphological, functional, and gene expression parameters in rats submitted to pulmonary artery banding compared to control rats, with the temporal evolution of these parameters, and to analyze the influence of RV
remodeling by pulmonary artery banding in rats and their controls over time on LV geometry, histology, gene expression, and functional performance. Methods: Healthy 6-week-old male Wistar-EPM rats weighing 170-200 g were included. One day after the echocardiogram, depending on the animals undergoing the pulmonary artery banding (PAB) procedure or not (control group), they were then randomly divided into subgroups according to the follow-up time: 72 h, or 2, 4, 6, or 8 weeks. In each subgroup, the following were conducted: a new echocardiogram, a hemodynamic
study, the collection of material for morphological analysis (hypertrophy and fibrosis), and molecular biology (gene expression). The results were presented as the mean ± standard deviation of the mean. A two-way ANOVA and Tukey post-test compared the variables of the subgroups and evolution follow-up times. The adopted significance level was 5%. Results: There was no significant difference among the subgroups in the percentage of water in both the lungs and the liver (the percentage of water in the lungs ranged from 76% to 78% and that of the liver ranged from 67% to 71%). The weight of the right chambers was significantly higher in PAB animals in all subgroups (RV PAB weighed from 0.34 to 0.48 g, and control subjects, from 0.17 to 0.20 g; right atrium (RA) with PAB from 0.09 to 0.14 g; and control subjects from 0.02 to 0.03 g). In the RV of PAB animals, there was a significant increase in myocyte nuclear volume (97 μm3-183.6 μm3) compared to control subjects (34.2 μm3-57.2 μm3), which was more intense in subgroups with shorter PAB follow-up time, and the fibrosis percentage (5.9%-10.4% vs. 0.96%-1.18%) was higher as the PAB follow-up time was longer. In the echocardiography result, there was a significant increase in myocardial thickness in all PAB groups (0.09-0.11 cm compared to control subjects-0.04-0.05 cm), but there was no variation in RV diastolic diameter. From 2 to 8 weeks of PAB, the S-wave (S\') (0.031 cm/s and 0.040 cm/s), and fractional area change (FAC) (51%-56%), RV systolic function parameters were significantly lower than those of the respective control subjects (0.040 cm/s to 0.050 cm/s and 61%-67%). Furthermore, higher expression of genes related to hypertrophy and extracellular matrix in the initial subgroups and apoptosis genes in the longer follow-up PAB subgroups were observed in RV. On the other hand, LV weight was not different between animals with and without PAB. The nuclear volume of the PAB animals was greater than that of the control subjects (74 μm3-136 μm3; 40.8 μm3-46.9 μm3), and the percentage of fibrosis was significantly higher in the 4- and 8-week PAB groups (1.2% and 2.2%) compared to the control subjects (0.4% and 0.7%). Echocardiography showed that the diastolic diameter and LV myocardial thickness were not different between PAB animals and control subjects. Measurements of isovolumetric relaxation time and E-wave deceleration time at the echocardiography were different between PAB animals and control subjects in all subgroups, but there were no changes in diastolic function in the hemodynamic study. There was also increased expression of genes related to various functions, particularly hypertrophy. Conclusion: 1) Rats submitted to pulmonary artery banding presented RV remodeling compatible with hypertrophy. Such alterations were mediated by increased gene expression and functional alterations, which coincide with the onset of fibrosis. 2) Structural changes of the RV, such as weight, myocardial thickness, myocyte nuclear volume, and degree of fibrosis, were modified according to the time of exposure to pulmonary artery banding and related to variations in gene expression, highlighting the change from an alpha to a beta pattern from early to late follow-up times. 3) The study suggests that the left ventricle developed histological alterations accompanied by gene expression modifications simultaneously with the alterations found in the right ventricle.