选择性β肾上腺素受体激动剂对人滑膜细胞增殖能力的影响  

The effects of the selective β-adrenergic receptor agonists on the ability of human synovial cell proliferation

作　　者：魏巍[1] 吴华勋[1] 付静静[1] 袁平凡[1] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物育部重点实验室,抗炎免疫药物协同创新中心,合肥230032

出　　处：《安徽医科大学学报》2015年第7期978-981,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81173075,81330081,81302784);安徽省科技攻关计划项目(编号:1301042098)

摘　　要：目的观察β-肾上腺素受体(AR)激动药对人成纤维样滑膜细胞(FLS)增殖的作用,探讨β-AR信号对人FLS功能的影响。方法组织块培养法培养人FLS;使用肿瘤坏死因子α(TNF-α)作为刺激剂,MTT法分别检测β1-AR选择性激动剂多巴酚丁胺和β2-AR选择性激动剂沙丁胺醇对人FLS增殖作用的影响,并计算增殖抑制率;使用沙丁胺醇+β2-AR选择性拮抗剂ICI 118551观察其对FLS增殖功能的影响;Western blot法检测人FLSβ-AR、G蛋白偶联受体激酶2(GRK2)和β抑制蛋白2(β-arrestin2)胞膜蛋白的表达水平。结果 TNF-α可以显著促进人FLS的增殖;β2-AR激动剂沙丁胺醇能明显抑制FLS的增殖,其拮抗剂ICI 118551能显著拮抗沙丁胺醇的作用;β1-AR选择性激动剂多巴酚丁胺对FLS的增殖无显著影响;TNF-α和沙丁胺醇均能显著降低β2-AR胞膜表达,上调GRK2、β-arrestin2的胞膜表达。结论β2-AR信号的激活可以抑制FLS增殖;TNF-α和沙丁胺醇可以使GRK2、β-arrestin2的胞膜表达增加,β2-AR胸膜表达下降。Objective To observe the function of β-adrenergic receptor （ AR） agonists on human fibroblasts syno-viocytes （ FLS） proliferation and explore the effect ofβ-AR signaling on FLS function. Methods Tissue culturing method cultured human FLS;using TNF-α as a stimulant;MTT method was used to detect the effect ofβ1-AR se-lective agonist dobutamine andβ2-AR selective agonist salbutamol on the proliferation of human FLS, and calculate the proliferation inhibition rate. β2-AR selective antagonist ICI 118551 was used to observe the effect on FLS prolif-eration; Western blot method could detect cell membrane protein expression level belonged to FLS β-AR,GRK2 and β-arrestin2 on human. Results TNF-αcould significantly promote the proliferation of FLS on human,β2-AR agonist salbutamol could significantly inhibit the proliferation of FLS, and its antagonist ICI 118551 could signifi-cantly inhibit salbutamol action. β1-AR selective agonist dobutamine had no significant effect on the proliferation of FLS;TNF-α and salbutamol significantly decreased β2-AR expression of cell membrane, and up-regulated GRK2 andβ-arrestin2 expression in cell membrane. Conclusion The activation ofβ2-AR signal can inhibit the prolifera-tion of FLS;TNF-α and salbutamol can increase the expression of GRK2,β-arrestin2,and decrease the expression of β2-AR in cell membrane.

关 键 词：肾上腺素受体 成纤维样滑膜细胞 沙丁胺醇 增殖 

分 类 号：R967[医药卫生—药理学]