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目的探讨去甲肾上腺素(NE)对内皮祖细胞(EPCs)增殖和迁移能力的调节作用及其分子机制。方法将培养的健康成人外周血EPCs用不同浓度的NE、肾上腺素能受体拮抗剂或MAPK信号通道阻滞剂干预,检测EPCs的增殖和迁移能力,以及ERK1/2信号通路的激活情况。结果 NE浓度依赖性地(0.01、0.1、1、10μmol/L)促进EPCs增殖,与对照组比较EPCs分别增加(48.3±23.3)%、(70.5±35.6)%、(82.4±14.9)%和(100.3±48.1)%。α受体拮抗剂酚妥拉明、选择性β2肾上腺能受体拮抗剂I127、JNK抑制剂SP600125和ERK1/2抑制剂A6355能够阻断NE的促增殖作用;而β1受体拮抗剂美托洛尔和p38抑制剂PD169318不能阻断NE的刺激效应。10μmol/L NE促进EPCs的迁移(P<0.05),10μmol/L酚妥拉明和10μmol/L I127能够阻断这种作用,但美托洛尔不能。NE能够浓度依赖性(0.1、1、10μmol/L)地激活EPCs内的ERK1/2,酚妥拉明和I127能够阻断ERK1/2激活(P<0.05),而美托洛尔不能。结论 NE可能通过α和β2肾上腺能受体激活ERK1/2促进EPCs的迁移和增殖。
Objective To investigate the regulatory effect of norepinephrine (NE) on the proliferation and migration of endothelial progenitor cells (EPCs) and its molecular mechanisms. Methods The EPCs in healthy adult human peripheral blood were intervened by different concentrations of NE, adrenergic receptor antagonist or MAPK signal channel blocker to detect the proliferation and migration of EPCs and the activation of ERK1 / 2 signaling pathway. Results EPCs could promote the proliferation of EPCs in a concentration - dependent manner (0.01,0.1,1,10μmol / L). Compared with the control group, EPCs increased the numbers of EPCs by (48.3 ± 23.3)%, (70.5 ± 35.6)%, (82.4 ± 14.9)% and 100.3 ± 48.1)%. α receptor antagonist phentolamine, selective β2 adrenergic receptor antagonist I127, JNK inhibitor SP600125 and ERK1 / 2 inhibitor A6355 can block the promotion of NE proliferation; and β1 receptor antagonist metoprolol Seoul and p38 inhibitor PD169318 failed to block the stimulatory effect of NE. 10μmol / L NE promoted the migration of EPCs (P <0.05), and 10μmol / L phentolamine and 10μmol / L I127 blocked this effect, but metoprolol did not. NE could activate ERK1 / 2 in EPCs in a concentration-dependent manner (0.1, 1, 10μmol / L). Phentolamine and I127 blocked ERK1 / 2 activation (P <0.05), while metoprolol failed. Conclusion NE may activate ERK1 / 2 through α and β2 adrenergic receptors to promote EPCs migration and proliferation.