摘要
目的:探讨血管紧张素II(Ang II)对单核细胞黏附的影响及机制研究。方法:Ang II(10-6 M)培养人单核细胞株4 h或24 h,并加入氯沙坦(1,3,10μM)或抗氧化剂吡咯烷二硫代氨基甲酸盐(PDTC,10μM),检测单核细胞内活性氧(ROS)水平、单核内皮细胞黏附、上清液中白细胞介素-8(IL-8)、肿瘤坏死因子α(TNF-α)水平、单核细胞的白细胞介素-8受体(CXCR2)mRNA表达以及核转录因子κB(NF-κB)和活化蛋白(AP-1)的活性。结果:Ang II(10-6M)孵育单核细胞后显著增加细胞内ROS水平、上清液中白细胞介素-8和肿瘤坏死因子α水平,单核细胞内核转录因子κB和AP-1的活性以及上调CXCR2 mRNA表达,促进单核细胞黏附到内皮细胞。预先给予氯沙坦呈浓度依赖性的抑制Ang II诱导的上述反应,抗氧化剂PDTC同样抑制Ang II诱导的氧化应激和单核细胞黏附。结论:Ang II通过上调CXCR2表达,增加单核细胞黏附,活化单核细胞促进动脉粥样硬化的发生,这一过程涉及ROS-NF-κB/AP-1通路。
Objective: To explore the effect of angiotensin Ⅱ (Ang Ⅱ) increasing the monocyte adhesion with the possible molecular mechanism.
Methods: The experimental human monocytoid cells (THP-1) were cultured in 4 groups, each group contained 1×10^6 cells. ① Blank control group, the cells were cultured for 4h or 24 h. ② Ang II treated group, the cells were cultured with Ang II (10-6 M) for 4h or 24 h. ③ Losartan treated group, the cells were cultured with losartan (1, 3, 10)μM for 1 hour and followed-by Ang II (10.6 M) for 4h or 24 h. ④ PDTC group, cells were cultured with the anti oxidative agent PDTC 10 μM for 1.5 h and followed by Ang Ⅱ(10^-6 M) for 4h or 24 h. The intracellular reactive oxygen species (ROS), the levels of interleukin-8 (IL-8), tumor necrosis factor (TNF-α in the medium and the adhesion of monocyte to endothelial cells were examined. The expression of CXCR2 mRNA, nuclear factor kappaB (NF-κB) activity and activated protein (AP-1) were determined and compared among different groups.
Results: Compared with Blank control group, the Ang II treated group had significantly elevated intracellular ROS, IL-8 and TNF-α, more monocyte adhesion to endothelial cells, higher expression of CXCR2 mRNA, increased activity of NF-κB and AP-1. The above Ang Ⅱ induced up-regulations were inhibited by losartan in a dose-dependent manner. PDTC may also inhibit the Ang Ⅱ induced oxidative stress and monocyte adhesion. Conclusion: Ang Ⅱ activates monocyte for developing atherosclerosis via up-regulating IL-8 receptor CXCR2expression, which might be involved in ROS-NF-κB/AP-1 pathway.
出处
《中国循环杂志》
CSCD
北大核心
2014年第5期367-371,共5页
Chinese Circulation Journal
基金
省科技厅课题(编号:2008FJ4183)
湖南省卫生厅课题(编号:B2010-013)