摘要
目的研究血管紧张素Ⅱ(AngⅡ)1型受体(AT1)拮抗剂厄贝沙坦对单核-巨噬细胞核因子-κB(NF-κB)活性和表达的影响,探讨厄贝沙坦抗动脉粥样硬化(AS)的作用机制。方法用不同浓度的厄贝沙坦预作用已诱导分化的单核-巨噬细胞2 h,再加入1×10-6mol/L的AngⅡ24 h后,用细胞免疫荧光染色检测单核-巨噬细胞表达NF-κB P65的阳性细胞率,采用电泳迁移率改变分析检测NF-κB的活性。结果单核-巨噬细胞NF-κBP65阳性表达率,AngⅡ组(65.2±7.2)%>0.01μmol/L厄贝沙坦组(47.2±5.8)%>0.1μmol/L厄贝沙坦组(32.7±3.6)%>1μmol/L厄贝沙坦组(15.2±4.1)%>空白对照组(8.1±3.0)%,组间两两比较差异均有统计学意义(P<0.05);NF-κB的活性,AngⅡ组>各浓度厄贝沙坦组>空白对照组(P<0.05),0.01μmol/L厄贝沙坦组、0.1μmol/L厄贝沙坦组均>1μmol/L厄贝沙坦组(P<0.05),0.01μmol/L厄贝沙坦组与0.1μmol/L厄贝沙坦组比较,差异无统计学意义(P>0.05)。结论厄贝沙坦可浓度依赖性地抑制AngⅡ诱导的单核-巨噬细胞NF-κB的活性和表达,其可能通过此作用抑制AS的启动环节,从而发挥抗AS作用。
Objective To evaluate the effects of irbesartan,a specific type of angiotensin Ⅱ receptor(AT1) antagonist,on nuclear factor-κB(NF-κB)activity and expression in cultured THP-1 cells.Methods Irbesartan was added to the culture medium for 2 hours before cells were incubated with AngⅡ(1×10-6 mol/L) for 24 hours.Positive cells of NF-κB P65 were detected by cellular immune fluorescence staining technique,and the activity of NF-κB was determined by electrophoretic mobility shift assay.Results The rate of NF-κB P65 positive THP-1 cells was(65.2±7.2)% in AngⅡ group,(47.2±5.8)% in 0.01 μmol/L irbesartan group,(32.7±3.6)% in 0.1 μmol/L irbesartan group,(15.2±4.1)% in 1 μmol/L irbesartan group,and(8.1±3.0)% in the control group,with significant difference between any two groups(P〈0.05).The relative activity of NF-κB was significantly higher in AngⅡ group than that in the control group and those in the three irbesartan groups(P〈0.05).The relative activity of NF-κB was significantly higher in 0.01 μmol/L irbesartan group and 0.1 μmol/L irbesartan group than that in 1 μmol/L irbesartan group(P〈0.05),with nonsignificant difference between 0.01 μmol/L irbesartan group and 0.1 μmol/L irbesartan group.Conclusion Irbesartan blocked AngⅡ-induced NF-κB activity and expression in THP-1 cells.This may be related to the mechanisms of anti-atherosclerotic properties of irbesartan.
出处
《中国全科医学》
CAS
CSCD
北大核心
2012年第20期2295-2297,共3页
Chinese General Practice
基金
山东省自然科学基金项目(Y2006C129)