| In recent years,the incidence and mortality of atherosclerotic coronary heart disease(CHD)have been gradually increasing.With the improvement of people's living standard in China,CHD has become a high incidence disease that endangers people's health and life expectancy.Coronary artery bypass grafting can relieve clinical symptoms such as chest tightness and palpitations to a certain extent,which is conducive to the improvement of patients' quality of life and the reduction of related oral drugs and examination costs.Although the vein bridge is easy to obtain and free,the long-term patency rate is still a difficult problem.Clinical analysis after 10 years of coronary artery bypass grafting(cabg),approximately 60% of patients require stenting and rethoracotomy.Therefore,the graft patency rate after great saphenous vein surgery is an important indicator to judge the long-term survival rate after bypass surgery.In this study proposed according to the related pathology mechanism of vascular stenosis,transplanted vein bridge SRT2104 specificity SIRT1 agonist,electrostatic spinning technology,the application will SRT2104 load in biodegradable vascular sheath,played a drug delivery system formed at the same time,reduce hemal wall shear stress and maintain blood vessel walls tension three advantages,thus to restrain vascular inflammation infiltration and endometrial hyperplasia.1: the biodegradable vessel sheath of plga-srt2104 nanofibers was prepared by electrostatic spinning and its physical and chemical properties were studiedObjective : The spinning prepared by electrostatic spinning device has many advantages such as nanometer diameter,excellent specific surface area,high porosity,reasonable uniformity,etc.,and is widely used in medical materials,tissue engineering,catalysis,protection and national defense.Electrostatic spinning method applied in this study for vascular sheath,first to explore the different levels of voltage for spinning spacing and the influence of the microstructure,thereby to explore the optimal delivery efficiency of spinning related physical parameters,and to explore the degradation efficiency of drug-loading vascular sheath to determine drug operation itself is a fundamental impact foreign sheath degradation efficiency.Methods:Electrostatic spinning is carried out at different voltages of 5KV,10 KV and 15 KV.By means of SEM observation,the spinning nanometer microstructure corresponding to different voltages was observed under the condition that the injection velocity and distance were equal.The unloaded vessel sheath and the drug-loaded vessel sheath were divided into two groups and placed in three steaming waters to compare the residual rates at each time point(1-7 weeks).Results:Under the voltage of 15 kv,the electrostatic spinning has continuous and balanced spinning under the electron microscope,with large gaps between the spinning,which can play a better role in carrying drugs.At the same time,in terms of degradation rate,Pl GA degrades faster and drug-carrying vessel sheath slows down.In the early stage of degradation(1-4 weeks),the degradation rate of PLGA is relatively balanced,and after a certain time(4 weeks),the degradation rate increases.At 7 weeks,PLGA degraded to 71.55±2.07% of its original mass,and plga-srt2104 to 78±1.96%.Pearson correlation coefficient between the two groups at each time point was p<0.05.2 : Study on the degradation of vascular sheath by plga-srt2104 nanofibers to inhibit the inflammatory infiltration and proliferation of intima after venous bridging in rabbitsObjective: to observe the sustained effect of sirt1 novel receptor agonist SRT2104 in vitro in a sustainably released manner,and to verify the inhibitory effect of SRT2104 biodegradable vascular sheath on the inflammation and proliferation of endovenous bridging vessels after jugular arteriovenous bypass in rabbits.Methods: 30 Zealand white rabbits(3-4 kg,male or female)were selected as the control group,and the non-drug loading external sheath and SRT2104 external sheath external venous bridging vessels were selected as the experimental group.Six in each group were selected to measure the inner diameter and blood flow peak at the immediate,1 and 8 weeks after the operation to calculate the corresponding change rate,and the intimal thickness and intimal medium membrane ratio of the bridge at the 8 weeks after the operation were measured.At the same time,immunofluorescence staining images of CD45,CD68 and ki-67 in each group 7 days after the operation were compared with the remaining 4 in each group,and the average fluorescence density was semi-quantitative and proliferative cell count was performed,and 2 fluorescence field counts were selected blind at the same magnification.Results: Compared with the control group and the non-drug-loaded sheath group,the SRT2104 group showed no significant changes in vessel diameter and flow velocity at 1 and 8 weeks after surgery(P<0.05 vs SRT2104 group).Histological examination showed that the intimal thickness of SRT2104 group decreased significantly compared with the control group and the non-drug loaded sheath group(P<0.01 vs SRT2104 group).At the same time,compared with the control group(P< 0.01)and non-drug loaded sheath group(P<0.05),the intima-media ratio was significantly reduced.In the immunofluorescence staining,compared with the control group,SRT2104 significantly inhibited the expression level of CD45(P < 0.01 VS SRT2104),and the vascular sheath also inhibited the infiltration of CD45(P < 0.01 VS non-drug sheath group).In terms of the degree of macrophage infiltration represented by CD68,there was no significant difference between the control group and the non-drug loading group(P >0.05),but there were significant differences between the control group and the SRT2104 group(P < 0.01 VS SRT2104 group).From the early postoperative proliferation indicators represented by ki-67,there were significant differences among the three groups.Compared with the other two groups,the proliferation of SRT2104 group was significantly lower(P < 0.01 VS SRT2104 group),and the difference between the control group and the non-drug loaded sheath group was also statistically significant(P < 0.01 VS non-drug loaded sheath group).Conclusion: SRT2104,as a novel sirt1 agonist,can inhibit the inflammatory infiltration and proliferation of endovascular membrane in the degradable vascular sheath. |
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