| Objective Coronary artery bypass grafting(CABG)is one of the common methods for the treatment of multiple coronary lesions.However,the restenosis of the vein after transplantation has seriously affected the prognosis and survival of patients,Postoperative restenosis of the bridging vein is a complex process involving multiple mechanisms,The research group through the establishment of rat model of jugular-carotid artery transplantation to simulate the process of restenosis after CABG;The use of highly selective P38 MAPK inhibitor SB203580 intervention;Explore the P38 MAPK pathway in the role of bridging vein restenosis,and take different ways to explore the appropriate drug administration methods.Methods 48 SD rats(male and female,12-14 weeks of age,weighing 250-300g)were randomly divided into four groups,mock surgical group(M),control group(C),one-time administration group(O administration)and continuous administration group(CA),There are 12 rats in each group.Sham-operated group only simulated the operation process,free vein,ligation of the branches,without disconnecting the jugular vein and transplanting the vascular operation.Control group ipsilateral jugular vein-carotid artery transplantation.One-time administration group was given SB203580 intragastrically 5mg / kg one hour before operation,then ipsilateral jugular vein-carotid artery transplantation.Rats in continuous administration group were given SB203580 intragastrically 3mg / kg after wake-up,and then ipsilateral jugular vein-carotid artery transplantation was performed.SB203580 intragastrically administered 3mg / kg once daily after operation.The blood vessels were removed 4 weeks after operation in each group,and the changes of the veins in each group were observed with the naked eye.Take fresh bridge vascular fixed preservation,HE staining,Masson staining,Through the microscope computer processing system to determine the intima and media thickness and collagen number,The levels of P38,P-P38 and a-sma in the transplanted blood vessels were determined by Western blotting WB.Immunohistochemistry was u s e d t o d e t e r m i n e t h e c o n t e n t o f a-s m a a n d P C N A i n transplanted blood vessels.Result Surgery are successful,Macroscopic observation 4 weeks after the removal of each group of blood vessels have varying degrees of granulation tissue proliferation,wall thickening and varying degrees of stenosis,of which the most serious group.HE stained by computer image system analysis shows: The thickness of intimal and mesangial hyperplasia in control group was significantly higher than that in blank group,one-time administration group and continuous administration group,the difference was statistically significant(P <0.05).The thickness of intimal hyperplasia in one-time administration group was significantly higher than that in continuous administration group and sham operation group(P <0.05).Western blotting showed that the protein levels of P38,P-P38 and a-sma in control group were significantly higher than those in blank group,once-administered group and continuous-administered group.The difference was statistically significant(P <0.05).The product of P38,P-P38 and a-sma in one-time administration group was significantly higher than that in continuous administration group and blank control group(P <0.05).The product of P38,P-P38,a-sma protein in continuous administration group was significantly higher than that in blank group,the difference was statistically significant(P <0.05).immunochemistry:A-sma immunohistochemistry showed that a small amount of positive cells were found in the intima,Vascular membrane and vascular adventitiaof the blank group,In the control group,a large number of positive cells were seen in the intima,media and adventitia,There was a moderate expression of positive cells in the single administration group and the continuous administration group,and the positive cells in the single administration group were higher than those in the continuous administration group,with statistical significance(P <0.05).PCNA immunohistochemistry showed:The expression of PCNA in the control group was stronger than that in the control group.The proliferative cell infiltration was found in the whole layer,.One-time administration group,sustained administration group in the media,the outer membrane of proliferating cells showed moderate expression,Proliferating cells from the media,the outer membrane to the intimal membrane metastasis.Conclusion The P38 MAPK pathway is involved in the process of vein arterialization and restenosis and plays an important role in this process.As an inhibitor of P38 MAPK,SB203580 is applied to rat autologous vein graft model and is effective in reducing the proliferation of intima and media and increasing the rate of vascular patency.And sustained oral administration than the preoperative administration of a one-time to reduce vascular hyperplasia better,It provides a new idea of gene level for the further study and prevention and treatment of restenosis of CVI after CABG and provides a reference for the way of using SB203580. |
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