ABSTRACT
Objective To expose the effect and its potential mechanism of vinpocetine (Vinp) on the restenosis of dia?betic grafted veins. Methods Thirty-six Sprague-Dawley rats were randomized into saline control group and Vinp treat?ment group. The autologous jugular vein to carotid artery transplantation was performed in diabetic model rats. Normal sa?line or Vinp were intraperitoneally injected. The rats were sacrificed at 0, 2 or 4 weeks after surgery, then the grafted veins were harvested. The pathological sections were used to detect the effect of Vinp on intimal hyperplasia. The protein expres?sion of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemical method, and which was described by cell proliferation index. The phosphorylation of NF-κB was detected by Western blot assay. Results The treatment of Vinp on intimal hyperplasia in vivo was significant at two weeks after surgery (17.06±5.10)μm versus control group (39.79±7.84μm, P<0.01), (30.94±5.18)μm versus (63.67±18.09)μm at four weeks after surgery (P<0.01). Vinp treatment effectively reduced the protein expression of PCNA [2 weeks:(21.07±1.38)%vs. (28.13±1.35)%,P<0.01;4 weeks:(31.73±1.38)%vs. (63.67 ± 18.09)%, P<0.01]. The treatment of Vinp inhibited phosphorylation of NF-κB at two weeks (1.08 ± 0.42 vs. 0.84 ± 0.12, P < 0.01). Conclusion Vinpocetine can effectively attenuate intimal hyperplasia in diabetic grafted veins, which might be related to its effect on inhibiting phosphorylation of NF-κB as well as inflammation.
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.