Out‑Patient Department, The Second Hospital of Shandong University, Jinan, Shandong 250000, P.R. China.
Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250000, P.R. China.
Mol Med Rep. 2020 Nov;22(5):3629-3634. doi: 10.3892/mmr.2020.11451. Epub 2020 Aug 21.
Phosphoinositide 3-kinase catalytic subunit δ isoform (P110δ) is mainly expressed in white blood cells. It is involved in T and B lymphocyte differentiation, maturation and the neutrophil chemotaxis process. Apolipoprotein E (ApoE) is an arginine‑rich alkaline protein, which is present in plasma chylomicron, low‑density lipoprotein and very low‑density lipoprotein. The present study aimed to determine the effects of P110δ deletion on myocarditis in ApoE‑/‑ mice. A mouse model of ApoE and P110δ double deletion was initially constructed; hematoxylin and eosin (H&E) staining was performed to detect the histological alterations in the mouse myocardium. Systolic and diastolic alterations, and alterations in the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were examined by electrocardiogram. Blood cell of ApoE and P110δ double mice was used to detect changes in white blood cells and monocytes. Western blotting was used to detect the expression levels of apoptosis‑associated proteins, whereas flow cytometry was used to detect the percentage of apoptosis. Morphological alterations in myocardial cells were observed under a microscope. The results of polymerase chain reaction demonstrated that double deletion mice were successfully constructed. H&E staining revealed that cells in the ApoE‑/‑ mice were spindle‑shaped; however, the nuclei were smaller in the double deletion mice. There was no change in cardiac contraction in normal mice; however, in double deletion mice, the systolic and diastolic contractions were markedly reduced. LVFS and LVEF were decreased compared with in the control group. Blood cell analysis indicated that the content of white blood cells and monocytes in the experimental group was significantly higher than that in the control group. Western blotting demonstrated that the expression levels of apoptotic proteins in double deletion mice were significantly higher compared with in the control group. Flow cytometry revealed that the apoptotic ratio was increased in double deletion mice compared with in the control group (42 vs. 21%). These findings suggested that deletion of P110δ may induce monocyte peritoneal infiltration and increase apoptosis, thus promoting the development of myocarditis.
磷酸肌醇 3-激酶催化亚单位 δ 同工型（P110δ）主要表达于白细胞中。它参与 T 和 B 淋巴细胞分化、成熟以及中性粒细胞趋化过程。载脂蛋白 E（ApoE）是一种富含精氨酸的碱性蛋白，存在于血浆乳糜微粒、低密度脂蛋白和极低密度脂蛋白中。本研究旨在探讨 P110δ 缺失对 ApoE-/-小鼠心肌炎的影响。首先构建 ApoE 和 P110δ 双缺失小鼠模型；采用苏木精和伊红（H&E）染色法检测小鼠心肌组织的组织学改变。通过心电图检测收缩压和舒张压变化以及左室短轴缩短率（LVFS）和左室射血分数（LVEF）的改变。采用血细胞计数法检测 ApoE 和 P110δ 双缺失小鼠白细胞和单核细胞的变化。采用 Western blot 检测凋亡相关蛋白的表达水平，采用流式细胞术检测细胞凋亡率。在显微镜下观察心肌细胞的形态变化。聚合酶链反应的结果表明，双缺失小鼠构建成功。H&E 染色显示，ApoE-/-小鼠的细胞呈梭形；然而，双缺失小鼠的细胞核较小。正常小鼠的心脏收缩无变化；然而，在双缺失小鼠中，收缩和舒张收缩明显减少。与对照组相比，LVFS 和 LVEF 降低。血细胞分析表明，实验组的白细胞和单核细胞含量明显高于对照组。Western blot 表明，双缺失小鼠中凋亡蛋白的表达水平明显高于对照组。流式细胞术显示，与对照组相比，双缺失小鼠的凋亡比例增加（42 比 21%）。这些发现表明，P110δ 的缺失可能诱导单核细胞腹膜浸润并增加凋亡，从而促进心肌炎的发展。
