| Objective: Cerebrovascular disease is one of the most common diseases in neurosurgery,with a very high rate of death and disability,which seriously threatens human life and health.How to treat cerebrovascular diseases more effectively and improve patient prognosis has become a key research area nowadays.Interventional therapy has become the main treatment for cerebrovascular diseases due to its advantages of less trauma and shorter recovery time for patients.Cerebrovascular stents,which are commonly used in clinical practice,are mainly made of non-degradable materials such as nickel-titanium and cobalt-chromium alloy.This kind of permanent stent exists in the patient’s body for a long time,bringing many problems such as endothelial inflammation reaction,overgrowth and lumen narrowing.Therefore,for the development of degradable stents is the inevitable choice for future cerebrovascular stents.Magnesium has a natural advantage among many biodegradable material options due to its good biocompatibility and relatively low price.However,the problems of rapid degradation and uneven corrosion also limit the application of magnesium alloys.The new magnesium alloy Mg-2Zn-0.5Nd(hereinafter referred to as ZN20)adds zinc to the magnesium alloy to enhance its physical properties and neodymium to extend the degradation time.The excellent comprehensive performance of ZN20 was shown in the preliminary theoretical study.Therefore,in this experiment,ZN20 will be chosen as the object of study to investigate its corrosion situation,biocompatibility and cytotoxicity to provide new possibilities to solve the problems caused by traditional permanent scaffolds.Methods: 1.Human umbilical vein endothelial cells(HUVEC cells)and human neuroblastoma cells(SH-SY5 Y cells)were cultured in vitro with ZN20 and AZ31(a conventional magnesium alloy material used for degradable scaffolds)in groups until different times.The effect of ZN20 on the growth and proliferation of the two cell types and the degree of inflammatory response was investigated by means of CCK-8 and ELISA assay,and a comparative study was made with AZ31;2.The corrosion and degradation of ZN20 and AZ31 were scanned by electron microscopy at different times to investigate the corrosion characteristics of the two materials;3.Healthy male SD rats were randomly divided into three groups: group A(sham-operated group),group B(ZN20 group)and group C(AZ31 group),six rats in each group.group B and group C were established as carotid ZN20 implantation model and carotid AZ31 implantation model(the length of alloy material was 10 mm * diameter 0.23 mm wire).Every 30 days,two rats were randomly selected from groups A,B and C,respectively,and their left common carotid artery and brain tissues implanted with the alloy material were executed after anesthesia and quickly removed for in vivo experimental studies.Biocompatibility was evaluated using section HE staining,immunohistochemistry and protein blotting.Results: 1.CCK8 results showed that ZN20 inhibited the proliferation of SH-SY5 Y cells,but the cells were still proliferating in general,AZ31 had more obvious inhibition on SH-SY5 Y cells;ZN20 had no obvious effect on the proliferation of HUVEC cells,AZ31 had more obvious inhibition on HUVEC cells;ELISA results showed that the ZN20 group and the control cell group There was no significant difference in the expression of inflammatory factors between the ZN20 group and the control cell group;the expression of TNF-α and IL-6 in the AZ31 group was different compared with the control SH-SY5 Y cell group at day 7(P<0.05).2.In the electron microscopy scan results,there was a significant difference in the corrosion of ZN20 and AZ31: ZN20 in the first day of light corrosion,in the third,five,seven days corrosion gradually obvious,but there is no large area corrosion off the situation,and corrosion is uniformly distributed in the form of points;while AZ31 showed obvious uneven corrosion from the first day,and the corrosion was serious in the following days,and the corrosion fell off in a large area from the fifth day;3.Western blot detection of Bcl-2 and Bax showed that Bax expression was lower and Bcl-2 expression was higher in the ZN20 group compared with the sham-operated group;Bcl-2 expression was lower but Bax expression was higher in the AZ31 group compared with the sham-operated group;there were differences in Bcl-2 and Bax protein expression levels in the ZN20 group compared with the AZ31 group;and in the immunohistochemical detection of PECAM-1/CD31(Platelet endothelial cell adhesion molecule-1)and VE-cad(vascular endothelia cell cadherin)showed slightly higher CD31 expression in the ZN20 group compared with the sham-operated group(P<0.05)and no difference in VE-cad expression;the AZ31 group showed insignificant changes in CD31 expression compared with the sham-operated group,while VE-cad expression increased(P<0.05),indicating that ZN20 has a beneficial effect on The results of HE staining sections showed that the AZ31 group showed reduced or even absent endothelium,and some of the endothelium and mesothelium were seen to be absent;the ZN20 group showed mild hyperplasia of endothelium and reduced thickness of mesothelium and epithelium.the results of HE staining and immunohistochemical analysis were consistent,and the ZN20 group had intact endothelial structure and showed certain pro-endothelial function.Conclusion: ZN20 has excellent corrosion resistance and degrades more uniformly and slowly compared with AZ31;ZN20 has good biocompatibility,low cytotoxicity,and low impact on cells and microenvironment during degradation,which makes it safer as cerebrovascular scaffold material;ZN20 has certain pro-endothelial effect and has a positive effect on vessel wall repair.In terms of acting as a cerebrovascular scaffold,ZN20 has obvious advantages over other materials and provides a possibility to solve the problems of traditional permanent scaffolds. |
PDF Full Text Request