β-肾上腺素能药物对人离体嗜中性白细胞释放超氧阴离子的影响和机制

Effect of β-adrenergic agents on the stimulus-induced superoxide anion generation in human neutrophils in vitro

目的:用人离体嗜中性白细胞研究新型β1-受体阻滞药(艾司洛尔和兰地洛尔)和β2-受体激动药(舒喘宁)对嗜中性白细胞释放超氧阴离子的影响及机制。方法:细胞色素C还原法测定3种肾上腺素能药物对3种刺激剂介导的嗜中性白细胞释放超氧阴离子量。抗原抗体法检测丝氨酸或苏氨酸磷酸化。结果:艾司洛尔呈浓度依赖性抑制花生四烯酸(AA)介导的嗜中性白细胞释放超氧阴离子;兰地洛尔增加N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(fMLP)介导的嗜中性白细胞释放超氧阴离子。舒喘宁呈浓度依赖性抑制fMLP和佛波豆蔻醚乙酸盐(PMA)介导的嗜中性白细胞释放超氧阴离子。艾司洛尔抑制AA介导的嗜中性白细胞释放超氧阴离子与其抑制嗜中性白细胞蛋白质的丝氨酸或苏氨酸磷酸化是一致的。结论:β-受体药对嗜中性白细胞释放超氧阴离子的影响与β-受体和被阻滞的强度无关。

Objective： To study the effects of 2 β1--adrcnergic receptor blockers （ esmolol and landiolol） and 1 β2-adrenergic receptor agonist （salbutamol） on the stimulus-induced superoxide anion generation in human ncutroplfils in vitro. Methods： Super6xide anion generation in human neutroplfils stimulated by 3 β-adrenergic agents was determined by using cytochrome C reduction assay. The stimulation of human neutrophils with 3 β-adrenerglc agents was induced by 3 stimuli, arachidonic acid （ AA）, N-formyl-medtlonyl-leucylphenylalanlne （fMLP）, and phorbol 12-myristate β-acetate （PMA）. The sefine/threonine phosphorylation in neutrophils was detected by using Western blotting. Results： Esmolol inhibited the supemxide anion generation induced by AA in a concentration-dependent manner. Lnadiolol increased the superoxide anion generation induced by fMLP. Salbutamol inhibited the superoxide anion generation induced by fMLP and PMA in a concentration-dependent manner. The inhibition of AA-induced superoxide anion generation by esmolol was parallel to that of serine / threonine phosphorylation in nbutrophils. Conclusion： The effect of β- adrenergic agents on stimulus - induced superoxide anion generation is independent on the types and blocking degree of β-adrenergic receptor.