糖基化终产物刺激大鼠骨髓内皮细胞表达细胞间粘附分子-1的机制探讨

目的:探讨糖基化终产物(AGEs)致内皮细胞表达细胞间粘附分子-1(ICAM-1)与自由基产生之间的关系。方法:内皮细胞(EC)用抗AGEs抗体、抗IL-1多抗、N-乙酰半胱氨酸(NAC)预处理1 h后AGEs作用6 h,测定IL-1、超氧化物歧化酶(SOD)、ICAM-1、内皮细胞-中性粒细胞粘附率。结果:AGEs刺激后ICAM-1表达增加[吸光度(A)为0.65-0.14 vs 0.11-0.02]的内皮细胞SOD活性降低[(0.69-0.19)10³U/L vs(1.71-0.42)10³U/L]。ICAM-1的增加可被抗AGEs抗体[吸光度(A)为(0.12-0.01)]、NAC[吸光度(A)为(0.11-0.05)]和抗ICAM-1抗体[吸光度(A)为(0.10-0.04)]抑制。外源性IL-1也可刺激内皮细胞表达ICAM-1[吸光度(A)为(0.72-0.23)]。结论:AGEs刺激内皮细胞表达ICAM-1可能与其导致细胞自由基的产生有关;AGEs还可通过刺激其他细胞产生细胞因子间接作用于EC,参与促进ICAM-1表达。

The mechanism ofintercellular adhesion molecule-1 expression in endothelial cells stimulated by advancedglycosylation end products

AIM： To explore the relationship between intercellular adhesionmolecule-1(ICAM-1)expression in endothelial cells(EC) and advanced glycosylation end products(AGEs) stimulation. METHODS: Murine bone marrow derived ECs was stimulated by AGEs after pretreated with anti-AGEs, anti-IL-1β and N-acetylcysteine(NAC),then SOD activity and ICAM-1 concentration and adhesion rate(AR) were evaluated. RESULTS: ECs which expressed ICAM-1[(0.65±0.14） vs （0.11±0.02）] induced by AGEs showed lower SOD activity [(0.69±0.19）×103 U/L vs （1.71±0.42）×103 U/L]. The ICAM-1 expression as well as the increase of AR caused by AGEs stimulation could be suppressed by anti-AGEs(0.12±0.01） and NAC(0.11±0.05）. Anti-IL-1β had no influence on these changes. CONCLUSION： AGEs could induce endothelial cells to express ICAM-1 in vitro, most probably due to the formation of free radicals. Besides, AGEs may stimulate other cells to secrete cytokines resulting in ICAM-1 expression in endothelial cells.