Effect and mechanisms of aspirin on rat cardial fibroblast proliferation induced by aldosterone / 军事医学

ABSTRACT

Objective To investigate the effects of aspirin(aspi) on rat cardiac fibroblasts (CFs) proliferation induced by aldosterone(ald) and the underlying molecular mechanisms .Methods Primary CFs from 1-3 day neonatal rats were digested by 0.08%trypsin and then purified by differential adhesion .The rats were divided into four groupscontrol group, DMEM medium ( free calf serum ) , ald group [ DMEM medium ( free calf serum ) +ald 1 ×10 -8 mol/L ] , aspi group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L+aspi 1.11 ×10 -6 mol/L] and spiro group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L +spiro 1 ×10 -6 mol/L].The morphology of CFs was assayed by HE staining methods .MTT Methods were used to measure cell proliferation .Western blotting was used to determine protein expression of TGF-β-Smad 2,3,4.Results HE Staining results showed that compared with the control group , ald activated cell proliferation and increased the cell division phase significantly (P<0.01).Compared with ald group, aspi+ald as well as spiro+ald could reduce cell division significantly ( P<0 .05 ) .MTT assay showed that compared with control group , ald could significantly improve the metabolism of MTT in CF (P <0.01).Compared with ald group, aspi +ald as well as spiro+ald could reduce the metabolism of MTT (P<0.01).Western blotting revealed that the expression levels of TGF-β-Smad 2, 3, 4 in CF were significantly increased by the stimulation of ald but were significantly reduced in aspi +ald and spiro+ald groups compared with ald group (P<0.01).Conclusion Aspi can inhibit the proliferation of CFs induced by ald,possibly by down-regulating the expression of Smad 2, Smad3 and Smad4.