| Objective Coronary artery bypass graft surgery (CABG) is still used as one of the major treatment for coronary atherosclerotic heart disease, especially for those patients with severe disease. While vein grafts are still mainly used for graft, but even if the operation process is very smooth, the occurrence of postoperative stenosis or occlusion in implants is still inevitable. Even though use of aspirin, statins, "no-touch" technique and application of external stents may offers a variety of choice for prevention of postoperative vein graft disease. In fact, for now how to gain an available long term patency rate in vein graft after CABG is still a major clinical problem. Our study try to reveal any effect of Pioglitazone (PIO) on intimal hyperplasia in rats vein graft model. And try to explore the possible mechanism, provide a reference for clinical application and scientific research.Methods 32 male Sprague-Dawley rats which weigh 220±20g, were randomly divieded into two groups, one group admisnistrated gastric gavage with 3 mg.kg-1.d-1 dose of PIO and the other received placebo (normal saline) one week before operation. Then the right common carotid arteries were reconstructed using homolateral external jugular veins in rats after one week pretreatment. The drugs treatment was continued after surgery and until vein grafts were harvested at the point of two or four week after surgery. For the subsequent analysis, one part of sample was cut to pathological section prepared for microscopic examination, and the photographs were made. And the neointima thickness was measured by Computer image analysis software. The other part of graft was serve to observe the activation of extracellular signal regulated protein kinases (ERK1/2) by performing western blot technology. And in vitro, in accordance with four in all as the blank control group (DMSO) and low dose group (10 μmol/L PIO+PDGF-BB) and high dose group (100 μmol/L PIO+PDGF-BB) as well as the negative control group (DMSO+PDGF-BB) to establish the human saphenous vein smooth muscle cells (HS-VSMCs) culture model, after 24 hours of treatment, cells proliferation was detected by the Cell Counting Kit-8 (CCK-8) assay. And for apoptosis examination, the terminal deoxynucleotidyl transferase-mediated deoxyuride-5’-triphosphate nick-end labeling staining (TUNEL) were performed.Results PIO treatment significantly attenuated intimal thickening compared with the the control group both at 2 week (as 8.56±1.64μm in PIO group versus 25.44±0.89 μm in SC group for each group n=8, P<0.01) and 4 week (as 10.51±1.47μm in PIO group versus 35.69±1.07μm in SC group for each group n=8, P<0.01) after veins transplantation. For western bolt expression detection, the vein grafts from rats after 2 week received graft operation were collected, the integrated density value ratio of the phosphorylating ERK1/2 compare with total ERK1/2 proteins in PIO group was less than that of SC group (by 0.91+0.01 verse 1.28+0.01,each group n=8, P<0.01), by the sample prepared from the implants. In vitro, PIO administration significantly reduced PDGF-induced cells proliferation from both low and high dose group compare with negative group(), but fail with blank control(P>0.05). In addition, the negative group was higher than blank control(P<0.01), there was no different between two dose of PIO(P>0.05). Furthermore, PIO increased cells apoptosis in both two dose groups(P<0.01), it seems to be low dose more effective than high dose (P<0.01).Conclusion PIO effectively improved intimal hyperplasia in grafted veins perhaps associated with the ability to suppress vascular smooth muscle cells (VSMCs) proliferation and enhance cells apoptosis, and might be related to the down regulation of ERK1/2 activation. |
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