The Effect Of S1P Receptor On VitB6 Protecting Posterior Cerebral Artery In Offspring Rats Against Isocarbophos And Its Mechanism

BackgroundOrganophosphorus pesticides are widely used in agriculture.It is reported that long-term low dose exposure to organophosphorus may cause vascular dysfunction and accelerate the formation of atherosclerosis.Epidemiology shows that chronic organophosphorus exposure can lead to impairment of neurocognitive function.Although it has been reported that organophosphorus has an effect on offspring,the mechanism is not clear.ObjectiveTo observe whether the effect of Isocarbophos on the structure and function of the posterior cerebral arteries of rats was impaired.To investigate whether VitB6 inhibiting the damage induced by Isocarbophos to offspring rats,and whether S1P receptor is involved in the process.MethodsFour-week-old healthy120 female and 60 male Sprague-dawley?SD?rats,were divided into saline group,Vitamin B6?VitB6?group,Fingomode group,Isocarbophos group,Isocarbophos+Vitb6 group,Isocarbophos+VitB6+Fingomode group.10 males and 20 females per group.The female rats at 16 weeks old were given medicine,and then caged with normal male rats.8 offspring rats were randomly selected in each group after feeded 8 weeks.?1?Blood analysis of arterial blood from offspring rats;?2?The offspring rats'plasma and posterior cerebral artery tissues were used to measure the oxidative indexes and inflammatory factors.?3?Observation of morphology,detection of functional changes and expression of casepase-3 in posterior cerebral arteries of offspring rats.?4?Detection of S1P receptor expression in plasma and posterior cerebral artery of offspring rats.?5?Immunofluorescence and Western blot were used to detect the expression of S1P receptor subtypes S1P₁ and S1P₂ in the rat posterior cerebral artery.?6?SPSS 20.0statistical software was used for analysis.All the results were expressed as mean±standard deviation?SD?.Multiple groups were compared using One-way analysis of variance?One-way ANOVA?.P<0.05 was considered statistically significant.Result?1?Compared with the control group,the posterior cerebral artery morphology ofthe offspring of the Isocarbophos treatment group was significantly damaged,and the vasodilation was significantly reduced?P<0.05?.?2?Compared with the Isocarbophos group,VitB6 significantly reduced the contentof CO2 in blood,plasma and vascular MDA and inflammatory cytokines in the offspring?P<0.05?.?3?Compared with the Isocarbophos group,VitB6 significantly decreased theexpression of Caspase-3 in vascular tissue?P<0.05?,and increased the content of NO and SOD?P<0.05?.?4?Compared with the Isocarbophos group,VitB6 significantly improved themorphological damage of the posterior cerebral artery in the offspring rats,and the vasodilation was also significantly increased?P<0.05?.?5?Compared with the Isocarbophos group,VitB6 significantly increased the S1Pcontent in the plasma and posterior cerebral artery of the offspring rats?P<0.05?.?6?Isocarbophos reduced the expression of S1P₁ and S1P₂ in the posterior cerebralartery of offspring rats,and the decrease of S1P₁ was more significant?P<0.01?.VitB6inhibited the damage caused by Isocarbophos,fingolimod inhibited S1P₁ receptor,and VitB6 significantly inhibited the inhibitory effect of VitB6 when treated with fingolimod?P<0.05?.Conclusion?1?Long-term,low-dose intragastric administration to mother rats can induceposterior cerebral artery injury in offspring rats;?2?VitB6 can inhibit the damage of the posterior cerebral artery of progeny ratsinduced by isoflurane,and this effect may be related to the S1P₁ receptor.