内源性过氧亚硝基阴离子介导脂多糖导致肺动脉内皮细胞损伤
谷振勇, 凌亦凌, 徐小虎, 朱铁年, 丛斌
汕头大学医学院.广东,汕头 515031;河北医科大学病理生理教研室.河北,石家庄 050017
摘要
LPS剂量依赖性地引起BPAECs诱生ONOO~(-)生成标志物硝基酪氨酸(NT)的荧光强度(即ONOO~(-))明显增多,NT阳性细胞数和百分率也明显增多或增高(P<0.05);iNOS选择性抑制剂氨基胍(AG)明显抑制LPS诱生ONOO~(-)增多(P<0.05),而NT阳性细胞数和百分率分别减少或降低,但无明显差异。在LPS作用下BPAECs培养上清中的MDA含量和LDH活性明显增多和增高,呈现剂量依赖性效应。加AG后MDA含量明显降低(P<0.001),LDH活性呈降低趋势。LPS可诱导BPAECs凋亡明显增多,用EB荧光染色后可见细胞染色质浓集、核变小等凋亡征象。AG可导致LPS引起的BPAECs凋亡明显减少,但仍明显高于溶剂组。LPS可导致BPAECs线粒体呼吸抑制及膜电位下降。
Endogenous peroxynitrite mediates lipopolysaccharide-induced injury in culturd puomonary artery endothelial cells
Gu Chenyong, Ling Yiling, Xu Xiaohu, Zhu Tienian, Cong Bin
Shantou University Medical College.Shantou 515031,Guangdong;China
Abstract
LPS (1, 5 and 10 #mu#g/ml) caused a marked increase in fluorescent intensity of NT in a dose-dependent manner, which was significantly increased compared to the vehicle group (P<0.01). The number and percentage of NT positive cells were markedly increased (both P<0.05 vs vehicle group). Aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), inhibited LPS-induced incrase in fluorescent intensity of NT in BPAECs. However, the number and percentage of NT positive cells had a tendency to reduce. LPS brought about an enhancement in MDA content and the activity of LDH in cultured supernatant. AG reversed the enhancement in MDA content induced by LPS (P<0.01). In contrast, AG had a marginal effect on the activity of LDH. LPS induced an increase in apoptotic rate in BPAECs in a dose-dependent manner. The number of apoptotic cells markedly increased as well. Some BPAECs stained with fluorescent probe ethidium bromide showed morphological features of apoptosis with chromatin condensation and nuclear fragmentation. AG reduced the apoptotic rate and the number of apoptotic cells, both of which were still higher than those of vehicle group (P<0.05).
Key words: Peroxynitrite lipopolysaccharide;Pulmonary;Artery;Endothelial cells
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引用本文:
谷振勇, 凌亦凌, 徐小虎, 朱铁年, 丛斌. 内源性过氧亚硝基阴离子介导脂多糖导致肺动脉内皮细胞损伤[J]. 生理学报 2003; 55 (4): .
Gu Chenyong, Ling Yiling, Xu Xiaohu, Zhu Tienian, Cong Bin. Endogenous peroxynitrite mediates lipopolysaccharide-induced injury in culturd puomonary artery endothelial cells. Acta Physiol Sin 2003; 55 (4): (in Chinese with English abstract).