KLF2在肺动脉高压大鼠肺组织中的表达及机制探讨

Expression of KLF2 in pulmonary tissue of rats with pulmonary hypertension and its mechanism

目的:观察野百合碱(MCT)诱导的肺动脉高压大鼠肺组织中KLF2及其相关因子的表达。方法:腹腔一次性注射MCT制作肺动脉高压大鼠模型,采用RT-PCR及Western blot检测肺组织中KLF2、核因子-κB(NK-κB)、血管内皮生长因子受体2(VEGFR2)、内皮素-1(ET-1)、一氧化氮合酶(eNOS)等各因子的表达变化。采用ELISA方法测定血清白介素-1β(IL-1β)、白介素-6(IL-6)及内皮素-1(ET-1)水平。采用硝酸还原酶法测定血清一氧化氮(NO)含量。结果:MCT组大鼠肺组织中KLF2及eNOS的表达水平较对照组显著降低;而NK-κB、VEGFR2及ET-1的表达水平较对照组显著增高。MCT组大鼠血清中IL-1β、IL-6及ET-1水平变化较对照组显著升高,而NO水平较对照组显著降低。Spearman相关性分析显示:KLF2与血清IL-1β(r=-0.617,P<0.05)、IL-6(r=-0.539,P<0.05)及ET-1(r=-0.881,P<0.05)呈显著负相关,而与NO呈显著正相关(r=0.721,P<0.05)。结论:野百合碱诱导的肺动脉高压大鼠肺组织中KLF2显著降低,KLF2可能参与肺血管内皮细胞炎症反应、血管重构及血管异常收缩等发病过程中。

Objective:To investigate the expression of KLF2 and its related factors in the lung tissues of rats with pulmonary hypertensionⅡnduced by monocrotaline(MCT).Methods:The rat model with pulmonary hypertension was made by one-time intraperitoneal injection of MCT.The expression of KLF2,NF-κB,VEGFR2,ET-1 and eNOS was detected in lung tissues of rats with pulmonary hypertension by RT-PCR and Western blot.The serum levels of IL-1β,IL-6 and ET-1 were measured by ELISA.Serum NO level was detected via nitrate reductase.Results:The expression of KLF2 and eNOS in the MCT group was significantly lower than that in the control group.The expression levels of NF-κB,VEGFR2 and ET-1 were significantly higher than those in the control group.The serum levels of IL-1β,IL-6 and ET-1 in the MCT group were significantly higher than those in the control group,while the level of NO was significantly lower than those in the control group.Spearman correlation analysis showed that KLF2 was negatively correlated with IL-1β(r=-0.617,P<0.05),IL-6(r=-0.539,P<0.05)and ET-1(r=-0.881,P<0.05),while positively correlated with serum NO(r=0.721,P<0.05).Conclusion:KLF2 in pulmonary tissues of rats with pulmonary hypertension induced by MCT is significantly decreased,and KLF2 may be involved in the pathogenesis of pulmonary vascular endothelial cell inflammation,vascular remodeling and abnormal vasoconstriction.