The Role Of Na~+-H~+ Exchanger 1 On Amorphous Nano-selenium Quantum Dots Inhibits Vascular Function Injury Induced By Isocarbophos

BackgroundOrganophosphorus pesticides are widely used in agriculture.It has been reported that atherosclerosis and other cardiovascular diseases and long-term low-dose exposure to organophosphorus-related organophosphorus can cause vascular dysfunction.The effect of hydroamidophos on cardiovascular function is a research hotspot,but the mechanism is not very clear.The effect of amorphous selenium on vascular function damage induced by hydroamidophos has not been reported in the literature.The role of sodium hydrogen exchange protein 1(NHE-1)in cardiovascular diseases has attracted more and more attention of researchers.The purpose of this study was to observe the inhibition of NHE-1 on hydroamidophos-induced posterior cerebral artery damage in rats by amorphous nano-selenium quantum dots(A-SeQDs).ObjectiveTo observe whether the structure and function of posterior cerebral artery were impaired after long-term low dose of hydroamidophos in rats.Whether A-SeQDs can inhibit the injury of the posterior cerebral artery induced by hydrazine in rats and to find evidence that NHE-1 participates in the inhibition of the injury of the posterior cerebral artery induced by hydrazine in rats by A-SeQDs.To explore the specific mechanism of organophosphorus injury to cardiovascular system,and to provide new ideas for the treatment of organophosphorus injury to vascular function.Method120 healthy male Sprague-Dawley(SD)rats aged 4 weeks were used.They were divided into saline group,amorphous selenium group,lithium chloride group,Isocarbophos group,Isocarbophos + Amorphous selenium group,Isocarbophos + A-SeQDs group,and Isocarbophos + Amorphous selenium + Lithium chloride group,with 6 rats in each group.0.5 mg/kg/2 day hydroamidophos was given orally for 16 weeks to establish the model.From the fifth week,50 mg/kg/day amorphous selenium was added to the drinking water of A-SeQDs group,Isocarbophos+A-SeQDs group,Isocarbophos+ A-SeQDs+LiCl group,and 1 mg/kg/day lithium chloride was added to the drinking water of LiCl group and Isocarbophos+A-SeQDs+LiCl group.After 16 weeks(1)arterial blood was taken for blood gas analysis;(2)plasma and posterior cerebral artery tissues were taken to detect oxidative indexes and inflammatory factors;(3)posterior cerebral artery was taken to observe the changes of vascular morphology,vascular function and Casepase-3 protein expression;(4)the expression of NHE 1 protein in posterior cerebral artery was detected by immunofluorescence and Western blot.(5)GraphPad Prism 5.0 statistical software was used to analyze the results.All measurements were expressed by Standard Deviation(SD).One-way ANOVA was used for comparison among groups,P < 0.05 had statistical significance.Result(1)Compared with the saline group,the morphology of the posterior cerebral artery was damaged and the vasodilation function was significantly reduced in the histamine group(P<0.05).Compared with the histamine group,the A-SeQDs intervention group significantly improved the structure of the posterior cerebral artery and increased the vasodilation function,but the improvement of A-SeQDs was not obvious when combined with LiCl.(2)Compared with saline group,total CO2,malondialdehyde(MDA),intercellular adhesion molecule-1(ICAM-1),Vascular cell adhesion molecule-1(VCAM-1),interleukin-1(IL-1),interleukin-6(IL-6)and C in histamine group were significantly higher than those in saline group.The expression of aspase-3 was significantly increased in the A-SeQDs intervention group.Compared with the isothion group,the total CO2 content in blood gas,MDA content in plasma and vascular tissue,ICAM-1,VCAM-1,IL-1,IL-6 content and Caspase-3 expression were significantly decreased in the A-SeQDs intervention group(P<0.05).When combined with LiCl,the decrease of A-SeQDs was not significant.(3)Compared with saline group,the contents of nitric oxide(NO)and superoxide dismutase(SOD)were significantly increased(P<0.05)in histamine group.Compared with histamine group,the contents of NO and SOD in A-SeQDs intervention group were significantly decreased(P<0.05).When combined with LiCl,the effect of A-SeQDs was not obvious.(4)Compared with saline group,NHE-1 content in plasma and posterior cerebral artery tissue of rats in histamine group was significantly decreased(P<0.01).Compared with histamine group,NHE-1 content in plasma and posterior cerebral artery tissue of rats was significantly increased by A-SeQDs(P<0.05).When combined with LiCl,the increase of A-SeQDs was not significant.(5)The expression of NHE-1 in rat posterior cerebral artery was significantly decreased by hydroamidophos(P<0.01);A-SeQDs inhibited the damage caused by hydroamidophos;A-SeQDs inhibited the damage caused by hydroamidophos,and A-SeQDs inhibited the damage caused by LiCl at the same time(P<0.05).Conclusion(1)Long-term and low-dose administration of hydroamidophos can induce vascular injury of posterior cerebral artery in rats.(2)A-SeQDs can inhibit the injury of posterior cerebral artery induced by hydrazine in rats,which may be related to NHE-1.