The Role Of Neopterin In The Pathogenesis Of Cerebral Infarction And Atherosclerosis And Its Possible Mechanism

Background:Acute ischemic stroke including cerebral thrombosis and cerebral infarction,cerebral thrombosis is the main pathological process,it is due to rough cerebral atherosclerosis lumen intima,luminal stenosis,when blood pressure is low,blood flow is slow,blood viscosity increased,platelet and clotting factors within the blood vessels condensed into pieces,form cerebral thrombosis.There is growing evidence shows that inflammatory processes and immune responses play a key role in the pathophysiology of atherosclerosis(plaque formation and detachment).Histological results have also demonstrated that the activation and interaction of monocytes,macrophages,and lymphocytes in plaques are important in the inflammatory process associated with plaque instability,and this complex interaction ultimately leads to plaque rupture.At present,the role of inflammatory response in acute coronary syndrome has been widely studied,but the effect on other arterial systems such as the carotid artery and cerebral artery is rarely reported.Neopterin(Npt),formation of an intermediate metabolites in the biosynthetic pathway of guanine nucleoside triphosphate,a relative biologically stable low molecular compounds,vitro experiments showed that T cells activity produced INF-? active monocyte/macrophages to secrete a large number of Neopterin,play a role of a variety of neurotransmitter cofactors of hydroxyl.In addition,it has been reported that Neopterin aggravates the inflammatory process in unstable plaque formation,and as a new indicator to predict the stability of atherosclerosis,which has played a significant role in the diagnosisand prognosis of coronary artery syndrome,while there is still no strong evidence for its effect on ischemic stroke.Objective:Through clinical trials,this study observed the correlation between Npt and inflammatory injury,nervous system injury and clinical risk factors of ischemic stroke,and focused on the role of Npt in the pathological process of atherosclerosis in ischemic stroke.Methods:The serum samples of normal people in the physical examination center were collected,the data and serum samples of patients with clinical cerebral infarction were collected,and the mouse model of cerebral infarction induced by the photochemical method was established.In the clinical trial,the control group were the normal people in the physical examination center and the experimental group were the stroke patients.The level of HDL,LDL,HCY,TG and white blood cells in the two groups were routinely checked,and the NIHSS score was analyzed.The serum Npt level was determined by ELISA.In the mouse model,6-8 weeks old mice were randomly divided into 4 groups with 30 mice in each group.Normal mice was control group,mice that were treated with nitrogen neon laser was laser group,mice that were treated with rhodamine were(drug group)and mice that were treated with nitrogen neon laser and rhodamine were treated as cerebral infarction group.The four groups of mice were scored by Bederson for correlation analysis,and then serum Npt level was detected by ELISA.Results:(1)Clinical trials showed that compare with control group,cerebral infarction patients' TG levels higher(P<0.01),LDL levels higher(P<0.01),HCY levels higher(P,0.01),HDL levels lower(P > 0.05),NIHSS score significantly higher(P<0.01),CRP levels higher(P<0.01),as shown in figure 1,confirm that during cerebral infarction onset level of inflammatory indicators increased significantly,while each risk factor levels was significantly elevated.(2)The Npt level(x±SE)in the cerebral infarction group was0.50±0.14ng/ml,and the Npt level(x±SE)in the control group was0.11 ± 0.02ng/ml.The serum Npt level in the cerebral infarction patients was significantly higher than that in the control group(P<0.01),and the il-23 level was also significantly higher,indicating that the inflammatory response was involved in the pathogenesis of cerebral infarction,as shown in figure 2.(3)Spearsman correlation analysis showed that the Npt level was positively correlated with NIHSS score(r=0.76,**P<0.01),as shown in figure 3,indicated that more severe neurological damage was,the higher the Npt level was.(4)Experiment showed that the expression of Npt in the cerebral infarction mice was significantly higher than that in the control group(P<0.01),which was statistically significant,as shown in figure 4.(5)Spearsman correlation analysis showed that the Npt level was positively correlated with 24 h Bederson score(r=0.876,**P<0.01),Npt level was positively correlated with 48 h Bederson score(r=0.837,**P<0.01),and Npt level was positively correlated with 72 h Bederson score(r=0.838,**P<0.01)),respectively,as shown in figure 5.It was further indicated that the higher the Bederson score of the cerebral infarction mice was,the more severe injury of the nerve function was,and the higher the serum Npt content was.Conclusion:Npt plays an important role in the pathogenesis of atherosclerosis in cerebral infarction.Npt can stimulate the generation of inflammatory factors,accelerate the occurrence of an inflammatory response,and then accelerate the formation of atherosclerotic plaque and the occurrence of cerebral infarction.