ABSTRACT
Objective To study the effect of Pioglitazone(PIO) on intimal hyperplasia after vein graft and its potential mechanism.Methods 32 male Sprague-Dawley rats were randomly divieded into two groups,one admisnistrated with PIO(3 mg· kg-1 · d-1) and the other with saline.A week later,the right common carotid arteries were reconstructed using homolateral external jugular veins in rats.The drugs treatment was continued after surgery for 2 or 4 weeks until grafted veins were harvested.The neointima thickness was measured by Computer image analysis software.To observe the activation of ERK1/2 pathway,the western blot were performed.In vitro,human great saphenous vein smooth muscle cells were co-cultured with PIO,and cells proliferation was detected by the CCK-8 assay.The TUNEL staining was performed to determine apoptosis.Results PIO treatment significantly attenuated intimal thickening compared with the the control group both at second [(8.56 ± 1.64) μm vs (25.44 ± 0.89) μm,P ＜ 0.01] and fourth week [(10.51 ± 1.47) μm vs (35.69 ± 1.07) μm,P ＜ 0.01)] after veins graft.Also PIO inhibited the ERK1/2 activation in grafted veins.In vitro,PIO significantly reduced PDGF-induced cells proliferation and increased cells apoptosis.Conclusion PIO effectively improved intimal hyperplasia in grafted veins perhaps associated with its ability to suppress vascular smooth muscle cells proliferation and enhance cell apoptosis,and might be related to the down regulation of ERK1/2 activity.
ABSTRACT
Objective To study the effect of Perfadex and Wisconsin Unviersity solution on the function of pulmonary artery endothelium.Methods Small lobe pulmonary arteries were dissected from nine porcine lungs.The artery from each lung was cut into six rings in 2mm.Two of them were randomly incubated in Krebs,Perfadex or Wisconsin Unviersity solution (UW solution) at 4℃ for 4 hours.Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation (percentage of-7.5 logM U46619 precontraction) induced by bradykinin or calcium ionophone A23187 in the present of indomethacin,L-NNA and oxyhemoglobin were measured at 37 ℃ in the organ chambers.Results Vasoconstriction induced by U46619 is no significant difference among three groups (P＞ 0.05).Compared with Krebs group,the relaxation induced by bradykinin or A23187 was significantly decreased in Perfadex group (P＜0.01),while there is no significant difference in UW group (P＞0.05).Conclusion Endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-mediated relaxation of porcine pulmonary artery.EDHF-mediated relaxation is impaired when the lung preserved with Wisconsin Unviersity solution,wheras its function is not affected by Perfadex solution.