摘要
目的探究尼可地尔对野百合碱(MCT)诱导肺动脉高压(PAH)大鼠肺动脉内皮细胞(PAECs)氧化损伤及肺动脉平滑肌细胞(PASMCs)增殖的影响。方法40只SD大鼠随机分成4组:对照组,MCT组,尼可地尔组和5-羟基葵酸(5-HD)组,每组10只。除对照组外均接受MCT诱导。取各组大鼠远端肺动脉组织并分离、培养PAECs和PASMCs。MTT法检测各组PASMCs增殖能力,并对PAECs活性氧簇(ROS)、一氧化氮(NO)、蛋白激酶C-ε(PKCε)、内皮型一氧化氮合酶(eNOS)和NADPH氧化酶(NOX)进行检测,评估PAECs氧化损伤情况。结果MCT组和5-HD组PAECs内ROS水平、PKCε相对表达水平和NOX活性均高于对照组,NO水平和eNOS相对表达水平均低于对照组(P<0.05)。尼可地尔组PAECs内ROS水平、PKCε相对表达水平均高于对照组,eNOS相对表达水平低于对照组,ROS水平、PKCε相对表达水平和NOX活性均低于MCT组和5-HD组,NO水平和eNOS相对表达水平均高于MCT组和5-HD组(P<0.05);培养48~72 h,MCT组和5-HD组PASMCs增殖能力均高于对照组和尼可地尔组(P<0.05)。72 h时,尼可地尔组PASMCs增殖能力高于对照组(P<0.05)。结论尼可地尔对MCT诱导的PAH大鼠PAECs氧化损伤具有保护作用,抑制了PASMCs增殖,钾离子通道开放可能是其作用机制。
Objective To investigate the effect of nicorandil on oxidative damage of pulmonary arterial endothelial cells(PAECs)and proliferation of pulmonary arterial smooth muscle cells(PASMCs)in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods A total of 40 SD rats were randomly divided into 4 groups:control group,MCT group,nicorandil group and 5-hydroxydecanoate(5-HD)group,10 rats per group.Except for control group,other groups were induced by MCT.Far-end pulmonary artery tissues of each group were collected and divided into PAECs and PASMCs for culture.MTT assay was used to investigate the proliferation of PASMCs.Reactive oxygen species(ROS),nitric oxide(NO),protein kinase C-ε(PKC-ε),endothelial nitric oxide synthase(eNOS)and NADPH oxidase(NOX)of PAECs were detected to assess the oxidative damage of PAECs.Results MCT group and 5-HD group had higher level of ROS,relative expression level of PKCεand activity of NOX and lower level of NO and relative expression level of eNOS than control group(P<0.05).Nicorandil group had higher level of ROS and relative expression level of PKCεand lower relatieve expression level of eNOS than control group;it also had lower level of ROS,expression level of PKCεand activity of NOX and higher level of NO and relative expression level of eNOS than MCT group and 5-HD group(P<0.05).During culture from 48~72 h,PASMCs of MCT group and 5-HD group had greater proliferation than control group and nicorandil group(P<0.05).At 72 h,PASMCs of nicorandil group had greater proliferation than control group(P<0.05).Conclusion Nicorandil has protective effect on oxidative damage of PAECs in MCT-induced PAH rats and suppresses the proliferation of PASMCs in MCT-induced PAH rats,and the mechanism might be related to the opening of potassium channel.
作者
陈静
杨海燕
毛亚飞
占焕平
魏宇峰
CHEN Jing;YANG Hai-yan;MAO Ya-fei;ZHAN Huan-ping;WEI Yu-feng(Department of Pharmacy,Zhoushan Women and Children′s Hospital,Zhoushan 316000,China;Department of Cardiology,Zhoushan Women and Children′s Hospital,Zhoushan 316000,China;Department of Medicine,Zhoushan Women and Children′s Hospital,Zhoushan 316000,China)
出处
《实用药物与临床》
CAS
2021年第6期486-490,共5页
Practical Pharmacy and Clinical Remedies
基金
浙江省医药卫生科技计划项目(2018KY857)。
关键词
肺动脉高压
大鼠
尼可地尔
野百合碱
肺动脉内皮细胞
肺动脉平滑肌细胞
Pulmonary arterial hypertension
Rat
Nicorandil
Monocrotaline
Pulmonary arterial endothelial cells
Pulmonary arterial smooth muscle cells
