解放军医学杂志2017，Vol.42Issue(4)：279-284,6.DOI:10.11855/j.issn.0577-7402.2017.04.02
MAPKs家族在中暑小鼠肺微血管内皮细胞凋亡中的作用及机制研究
Effects of MAPKs signaling on heat stress-induced apoptosis of pulmonary microvascular endothelial cells and its mechanism
摘要
Abstract
Objective To investigate the effect of mitogen-activated protein kinases (MAPKs) activation on the heat stressinduced apoptosis of pulmonary microvascular endothelial cells (PMVECs).Methods A mouse model of severe heat stroke was made and TUNEL and immunohistochemistry were employed to detect lung tissue damage.MACS separation was used for isolation of neonatal PMVECs,and TUNEL was utilized to detect the apoptosis of PMVECs.Western blotting was used for determining the MAPKs activation during heat stress recovery (0,2,6h).The monolayer permeability of endothelial cells was detected in terms of transmembrane resistance (TEER) and horseradish peroxidase (HRP).Cells were pretreated with MAPKs activation inhibitors to examine the effect of heat stress on the monolayer cell permeability and apoptosis.Results In mice with severe heat stroke,extensive apoptosis of PMVECs was found in their pulmonary tissues.TUNEL revealed that the number of apoptotic cells increased over time during heat stress recovery period and heat stress could activate MAPKs in PMVECs.Compared with heat stress group,in the cells pretreated with p38 or ERK activation inhibitor PD98059 and SB203580,the monolayer permeability and apoptosis increased while in cells pretreated withJNK inhibitor SP600125,the cellular permeability and apoptosis decreased.Conclusion In mice with severe heat stoke,PMVECs might experience apoptosis and p38 and ERK could inhibit apoptosis while JNK could promote apoptosis.关键词
中暑/肺微血管内皮细胞/丝裂原活性蛋白激酶类/细胞凋亡/细胞通透性Key words
heat stroke/pulmonary microvascular endothelial cells/mitogen-activated protein kinases/apoptosis/cell permeability分类
医药卫生引用本文复制引用
刘亚楠,徐秋林,郭晓华,周耿标,王郑莲,童华生,陆杰富,邱俊铭,苏磊..MAPKs家族在中暑小鼠肺微血管内皮细胞凋亡中的作用及机制研究[J].解放军医学杂志,2017,42(4):279-284,6.基金项目
国家自然科学基金(81671896,81471839) （81671896,81471839）
南方医科大学南方医院院长基金(2016C016)This work was supported by the National Natural Science Foundation of China (81671896,81471839),and the Foundation of President of Nanfang Hospital of Southern Medical University (2016C016) （2016C016）
