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

The mechanism of intercellular adhesion molecule-1 expression in endothelial cells stimulated by advanced glycosylation end products

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 - 1β多抗、N -乙酰半胱氨酸 (NAC)预处理 1h后AGEs作用 6h ,测定IL - 1β、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 14vs 0 11± 0 0 2 ]的内皮细胞SOD活性降低 [( 0 69± 0 19)× 10 3U/Lvs ( 1 71± 0 42 )× 10 3U/L]。ICAM - 1的增加可被抗AGEs抗体 [吸光度 (A)为 ( 0 12± 0 0 1) ]、NAC[吸光度 (A)为 ( 0 11± 0 0 5 ) ]和抗ICAM- 1抗体 [吸光度 (A)为 ( 0 10± 0 0 4 ) ]抑制。外源性IL - 1β也可刺激内皮细胞表达ICAM - 1[吸光度 (A)为 ( 0 72±0 2 3 ) ]。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。

AIM: To explore the relationship between intercellular adhesion molecule-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)×10 3 U/L vs (1.71±0.42)×10 3 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.