Department of Cardiovascular Medicine, Dongzhimen Hospital Affiliated to Beijing University of Traditional Chinese Medicine, Beijing, PR China.
Department of Cardiovascular Medicine, Dongzhimen Hospital Affiliated to Beijing University of Traditional Chinese Medicine, Beijing, PR China.
Biochem Biophys Res Commun. 2019 Jun 25;514(2):450-455. doi: 10.1016/j.bbrc.2019.04.129. Epub 2019 May 1.
To explore the regulation of PLA2G7 silencing on myocardial fibrosis in mice with coronary atherosclerosis, we established model of atherosclerosis using ApoE knockout mice, and set up a normal group. The successfully modeled mice were assigned into the following three groups: PLA2G7 silencing (shRNA) group, negative control (NC) group and blank group. Peripheral blood and myocardial tissue of each group of mice were harvested. The expressions of serum total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in mice were determine using Elisa, and the atherosclerosis index was calculated. The pathological changes of myocardial tissue were observed after HE staining. The collagen volume fraction in myocardium was determined with the use of Masson staining. The expression of PLA2G7 in myocardial tissue as well as myocardial fibrosis markers C-reactive protein, interleukin-6 and intercellular adhesion molecule-1 in each group were detected by qRT-PCR and Western blot. The area of thoracic aorta injury was detected after oil red O staining. Compared with the normal group, the levels of total cholesterol, triglyceride and LDL-C were increased, HDL-C levels were decreased, and atherosclerosis index was increased in the PLA2G7 shRNA group, NC group and blank group (all P < 0.05). The pathological state of myocardial tissue in the other three groups (except for the normal group) was obvious, but the PLA2G7 shRNA group showed certain improvement as compared with the blank group and the NC group (all P < 0.05). Compared with the NC group, the PLA2G7 shRNA group had significantly decreased collagen volume fraction, myocardial fibrosis and area of thoracic aorta injury (all P < 0.05). In conclusion, PLA2G7 silencing can improve the myocardial fibrosis in mice with coronary atherosclerosis, and PLA2G7 is expected to be a potential target for coronary atherosclerosis.
为了探讨 PLA2G7 沉默对动脉粥样硬化合并冠心病小鼠心肌纤维化的调控作用，我们使用 ApoE 基因敲除小鼠建立了动脉粥样硬化模型，并设立了正常组。将成功建模的小鼠分为 PLA2G7 沉默（shRNA）组、阴性对照组（NC 组）和空白组。采集各组小鼠外周血和心肌组织，采用 ELISA 法检测小鼠血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）的表达水平，并计算出动脉硬化指数。HE 染色观察心肌组织的病理变化，Masson 染色法测定心肌组织胶原容积分数。采用 qRT-PCR 和 Western blot 检测各组小鼠心肌组织 PLA2G7 表达及心肌纤维化标志物 C 反应蛋白、白细胞介素-6 和细胞间黏附分子-1 的表达。油红 O 染色检测胸主动脉损伤面积。与正常组比较，PLA2G7 shRNA 组、NC 组和空白组总胆固醇、三酰甘油、LDL-C 水平升高，HDL-C 水平降低，动脉硬化指数升高（均 P < 0.05）。除正常组外，其余三组小鼠心肌组织病理状态均较明显，但 PLA2G7 shRNA 组较空白组和 NC 组有一定改善（均 P < 0.05）。与 NC 组比较，PLA2G7 shRNA 组胶原容积分数、心肌纤维化和胸主动脉损伤面积均明显减小（均 P < 0.05）。综上所述，PLA2G7 沉默可改善动脉粥样硬化合并冠心病小鼠的心肌纤维化，PLA2G7 有望成为冠心病的潜在治疗靶点。
