Ma Qi-Lin, Yang Tian-Lun, Sun Ming, Li Yuan-Jian, Tang Can-E, Peng Zhen-Yu, He Shi-Lin, Chen Fang-Ping
FDepartment of Haematology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhonghua Xue Ye Xue Za Zhi. 2007 Sep;28(9):605-8.
To study the effects of insulin like growth factor-1 (IGF-1) on cell viability and tissue factor (TF) in angiotensin II (Ang II) induced vascular endothelial cells and to investigate its mechanisms.
10(-6) mol/L Ang II was added to human vascular endothelial cells (HUVECs) culture media alone or 30 min after pretreatment with IGF-1 (0.1 microg/ml , 0.5 microg/ml, 2.5 microg/ml). Cell viability and AngII type 1 receptor (AT1-R) mRNA were evaluated after 24 h incubation with AngII. At the optimum concentration of IGF-1 affecting cell viability, the time dependent manner for 12 - 48 h incubation with Ang II was evaluated. TF, NOS and NO were investigated after 24 h incubation with Ang II. In addition, NO synthase inhibitor Nomega-nitro-1-arginine methylester(L-NAME) was added 30 min before addition of IGF-1 and Ang II, and cell viability, TF, AT1-R mRNA, NOS and NO were evaluated after 24 h incubation.
(1) Ang II induced a decrease in cell vitality, an upregulation of AT1-R mRNA, an increase in TF, and a decrease in the activity of NOS and content of NO. (2) Pretreatment with IGF-1 significantly inhibited the decreased cell viability and upregulation of AT1-R mRNA. IGF-1 at 0.5 microg/ml showed the most obvious effects. This effect of cell viability recovery was in a time dependent manner during 12 -48 h. (3) IGF-1 also inhibited the increased content of TF, the decreased activity of NOS and the decreased content of NO. (4) The beneficial effects of IGF-1 on cultured endothelial cells were completely abolished by L-NAME.
IGF-1 pretreatment could enhance the ang II injured cell viability and anti-thrombosis capacity, and the protective effects may be related to activation of NOS-NO signaling pathway which inhibited AT1-R.
研究胰岛素样生长因子-1(IGF-1)对血管紧张素II(Ang II)诱导的血管内皮细胞活力及组织因子(TF)的影响,并探讨其作用机制。
将10⁻⁶mol/L的Ang II单独加入人血管内皮细胞(HUVECs)培养基中,或在IGF-1(0.1μg/ml、0.5μg/ml、2.5μg/ml)预处理30分钟后加入。与Ang II孵育24小时后,评估细胞活力和血管紧张素II 1型受体(AT1-R)mRNA水平。在影响细胞活力的IGF-1最佳浓度下,评估与Ang II孵育12至48小时的时间依赖性。与Ang II孵育24小时后,检测TF、一氧化氮合酶(NOS)和一氧化氮(NO)。此外,在加入IGF-1和Ang II前30分钟加入一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME),孵育24小时后评估细胞活力、TF、AT1-R mRNA、NOS和NO。
(1)Ang II导致细胞活力下降、AT1-R mRNA上调、TF增加、NOS活性降低和NO含量减少。(2)IGF-1预处理显著抑制细胞活力下降和AT1-R mRNA上调。0.5μg/ml的IGF-1效果最明显。这种细胞活力恢复作用在12至48小时内呈时间依赖性。(3)IGF-1还抑制TF含量增加、NOS活性降低和NO含量减少。(4)L-NAME完全消除了IGF-1对培养内皮细胞的有益作用。
IGF-1预处理可增强Ang II损伤的细胞活力和抗血栓形成能力,其保护作用可能与激活抑制AT1-R的NOS-NO信号通路有关。