激活AMPK抑制气道平滑肌细胞增殖的作用及机制研究

Objective: To clarify whether activation of adenosine monophosphate-activated protein kinase (AMPK) inhibits airway smooth muscle cells (ASMCs) proliferation and further to address the molecular mechanisms. Methods: Primary cultured ASMCs were treated with different concentrations of platelet-derived growth factor (PDGF) and metformin for different times. Concentrations and times that were most suitable for treatment were selected by the BrdU incorporation assay, and ASMCs were divided into the control group, PDGF group, metformin+PDGF group, AMPK siRNA+metformin+PDGF group and control siRNA+metformin+ PDGF group. BrdU incorporation in cells was measured and the protein level of t/p-AMPK, Skp2 and p27 were analyzed by western blot. Results: PDGF dose- and time-dependently stimulated ASMCs proliferation, this was accompanied with increased Skp2 expression and reduction of p27 protein. Preincubation of cells with metformin induced p-AMPK increased (P<0.05 versus control group), suppressed PDGF-stimulated ASMCs proliferation, and inhibited PDGF-caused changes of Skp2 and p27 protein level (P<0.05 versus PDGF group). Transfection of ASMCs with AMPK specific siRNA reversed the effects of metformin on Skp2 and p27 protein expression and cells proliferation. Conclusions: This study suggests that activation of AMPK has potential value in the management of asthma by inhibiting ASMCs proliferation therefore modulation of airway remodeling.