Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Ultrasound, The First Hospital of Qinhuangdao, Qinhuangdao, China.
Clin Exp Pharmacol Physiol. 2021 Apr;48(4):563-574. doi: 10.1111/1440-1681.13449. Epub 2020 Dec 21.
An efficient animal model is fundamental for studies on the underlying mechanisms of constrictive pericarditis (CP). A novel CP rat model was established by pericardial injection composing of lipopolysaccharides (LPS) and talcum powder without thoracotomy. Pathological changes were confirmed by histological staining. E-flow Doppler of mitral valve, tissue Doppler E' in the medial mitral annular (E' ) and the lateral mitral annular (E' ) were measured to assess ventricular filling function. Circumferential, longitudinal, and radial strains (SC, SL and SR) and the respective strain rates (SrC, SrL and SrR) were analyzed in interventricular septum (IVS) and left ventricular free wall (LVFW). Rat cardiac fibroblasts (CFs) were treated with LPS. The activation of transforming growth factor β1 (TGF-β1) was confirmed by Q-PCR and western blot assays. Thickening of pericardium and fibrosis in pericardium and subepicardial myocardium were showed in the model group. Diastolic dysfunction in the CP group was indicated by decreased E' and E' /E' , increased E/E' , decreased E of SrC and SrL, increased A and decreased E/A of SrC, SrL and SrR. Systolic dysfunction was indicated by decreased SC and SL in CP rats. The levels of TGF-β1, p-Smad2/3, α-smooth muscle actin (α-SMA), and collagen-I/III (COL-I/III) were increased in the CP group. The increased TGF-β1 that induced by LPS activated and phosphorylated Smad2/3 resulting in the secretion of α-SMA and COL-I/III. This model is of vital importance in studying the pathogenesis of CP.
一个高效的动物模型对于研究缩窄性心包炎（CP）的潜在机制至关重要。通过心包注射脂多糖（LPS）和滑石粉而无需开胸，建立了一种新型 CP 大鼠模型。通过组织学染色证实了病理变化。通过测量二尖瓣的 E-flow 多普勒、内侧二尖瓣环（E'）和外侧二尖瓣环（E'）的组织多普勒 E'，评估心室充盈功能。分析室间隔（IVS）和左心室游离壁（LVFW）中的环向、纵向和径向应变（SC、SL 和 SR）以及相应的应变率（SrC、SrL 和 SrR）。用 LPS 处理大鼠心肌成纤维细胞（CFs）。通过 Q-PCR 和 Western blot 检测证实转化生长因子β1（TGF-β1）的激活。模型组显示心包增厚和心包及心外膜下纤维化。CP 组 E' 和 E'/E'降低，E/E'增加，SrC 和 SrL 的 E 降低，SrC、SrL 和 SrR 的 A 增加，E/A 降低，表明舒张功能障碍。CP 大鼠的 SC 和 SL 降低，表明收缩功能障碍。CP 组 TGF-β1、p-Smad2/3、α-平滑肌肌动蛋白（α-SMA）和胶原 I/III（COL-I/III）水平升高。LPS 诱导的 TGF-β1 激活并磷酸化 Smad2/3，导致 α-SMA 和 COL-I/III 的分泌。该模型对于研究 CP 的发病机制具有重要意义。
