伊贝沙坦对脂多糖诱导血管内皮细胞核因子-κB激活及炎症因子表达的影响

Effect of irbesartan on LPS-induced NF-κB and ICAM-1 and TNF-α expression in human endothelium

目的 :观察血管紧张素Ⅱ 1型受体 (AT1R)拮抗剂伊贝沙坦 (Irb)对脂多糖 (LPS)诱导的体外培养人脐静脉血管内皮细胞 (HUVEC)核因子 κB(NF κB)激活与肿瘤坏死因子 α(TNF α)、细胞间粘附分子 1(ICAM 1)表达的影响。方法 :体外培养的第 3～ 5代HUVEC用于实验。用免疫组织化学分析检测细胞NF κB亚单位p6 5、ICAM 1的表达程度 ,酶联免疫吸附法检测培养液上清TNF α浓度。 结果 :LPS有效激活NF κB并诱导HU VEC表达TNF α、ICAM 1增加 ;Irb预先孵育 2h能抑制NF κB并减轻LPS诱导的HUVECTNF α和ICAM 1表达。结论 :LPS可能通过激活NF κB使TNF α、ICAM 1表达增加损伤血管内皮功能 ;Irb能保护因感染而致心血管疾病中的血管内皮功能 ,至少部分通过抑制NF κB这一途径而降低血管内皮TNF α、ICAM 1表达。

Objective:To investigate the effect of angiotensin Ⅱtype 1 receptor antagonist irbesartan (Irb) on the expression of intercellular adhesion molecule 1 (ICAM 1), tumor necrosis factor α(TNF α)and nuclear factor kappa B (NF κB) by lipopolysaccharide (LPS) in cultured human umbilical vein endothelial cells (HUVEC).Methods: Cultured passage 3～5 of HUVEC in vitro were stimulated with LPS, or incubated Irb 2 hr before LPS infusion, then cocultured suitable time. The expression of ICAM 1 and NF κB subunit p65 were evaluated by immuncytochemistical method and the production of TNF α was detected by ELISA.Results: Pretreatment of HUVECs with Irb inhibited LPS induced expression of ICAM 1 and TNF α in a dose dependent manner. The activation of NF κB by LPS is suppressed by Irb in a dose dependent manner.Conclusion: Irb can inhibit the LPS induced expression of ICAM 1 and TNF α through the inhibition of NF κB activation. Irb may also suppress the immune or inflammatory reaction of HUVEC responsible for endotoxin, which could be one possible explanation for the causes of the infection and inflammation observed for patients with cardiovascular disease.