摘要
目的观察γ-干扰素(IFN-γ)对血管内皮氧化应激损伤的保护作用,并评价26S蛋白酶体在其中的作用。方法建立由过氧化氢(H2O2)诱导的血管内皮氧化应激损伤细胞及离体器官模型,以细胞培养上清液中乳酸脱氢酶(LDH)及丙二醛(MDA)浓度评价血管内皮细胞(VEC)的损伤程度,以内皮依赖性血管松弛反应评价离体器官水平VEC的损伤程度。结果H2O2。可呈剂量依赖性和时间依赖性引起VEC损伤,表现为细胞培养上清液中LDH及MDA浓度增加(P〈0.05或P〈0.01),由乙酰胆碱(Ach)诱导的血管内皮依赖性松弛反应明显降低,表现为10^-5mol/LAch引起血管最大舒张反应由(95.82±9.25)%降至(12.61±2.96)%(P〈0.01);采用20ug/LIFN-γ预孵育VEC48h后可明显降低由H2O2引起的LDH及MDA生成(P均〈0.05),改善内皮依赖性血管松弛反应,由Ach诱导的血管最大舒张反应增至(72.68±18.82)%(P〈0.01);26S蛋白酶体抑制剂lactacystin可取消由IFN-γ诱导的内皮抗氧化保护作用。结论IFN-γ可诱导血管内皮对氧化应激的保护,其机制与26S蛋白酶体有关。
Objective To observe the protective effects of interferon-γ (IFN-γ) on hydrogen peroxide (H202)-induced oxidative injury to vascular endothelial cell (VEC), and to explore the role of 26S proteasome protection against IFN-γ-induced endothelial oxidative injury. Methods A H2O2-indueed VEC oxidative injury to cell and isolated organ models were reproduced in the current study. The VEC oxidative damage in cellular level was evaluated by the contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in culture medium, and the degree of oxidative injury of VEC in isolated organ level was evaluated by acetylchotine (Ach)-induced endothelium-dependent vascular relaxation. Results H2O2 triggered the oxidative injury in cultured VEC in a dose- and time-dependent manner, characterized by an increased contents of LDH and MDA in culture medium (P〈 0.05 or P 〈 0.01). The Ach-indueed endothelium- dependent vascular relaxation was decreased, and as shown by a decrease in 10^-5mol/L Ach induced maximum reaction of relaxation of vasculature from (95.82±9.25)% to (12.61±2.96)% (P〈0.01). The damage to VEC induced by H202 was diminished significantly after incubation with IFN-γ (20ug/L) for 48 hours, characterized by a decreased production of LDH and MDA (both P〈0.05) and restoration of endothelium-dependent vasodilation, and Ach-induced maximum reaction of vascular relaxation was increased to (72.68± 18.82)% (P〈0.01). 26S proteasome inhibitor lactacystin could partly antagonize the protective effects of IFN-γ on H2O2 induced oxidative injury. Conclusion IFN-γ possesses protective effects on H2O2-induced oxidative injury to vascular endothelium, and its mechanism is at least partly related with 26S proteasome.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2009年第9期540-543,共4页
Chinese Critical Care Medicine
基金
重庆市自然科学基金项目(CSTC,2008BB5106)
关键词
血管
内皮
氧化应激
Γ-干扰素
vascular
endothelium
oxidative stress
interferon-γ