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SP600125 Attenuates TLR4/MyD88/JNK Signaling Pathway-mediated Electromagnetic Pulse(EMP) Brain Injury

Posted on:2020-09-13Degree:MasterType:Thesis
Country:ChinaCandidate:Q NieFull Text:PDF
GTID:2404330596986440Subject:Anesthesia
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Nowadays,with the development of electronic technology,people are facing new challenges from time to time.The physiological effect of electromagnetic field?EMF?is undoubtedly an unavoidable damage for a particular group of people[1].Due to the increasing coverage of electronic equipment,the proportion of electromagnetic radiation in the causes of occupational-related diseases is also increasing day by day[2].Thus,EMF is closely related to human health.Electromagnetic pulse?EMP?is a radiation form of EMF.It has very short voltage rise time and high voltage pulse with ultra-wide spectrum,whose physical characteristics may cause radiation damage to exposed personnel[3,4].The purposes of this series of experiments include:1.The mechanism of brain injury and behavioral changes in SD rats after EMP irradiation;2.The role of JNK pathway in brain injury induced by EMP irradiation;3.The effect of JNK specific inhibitor SP600125 on brain injury induced by EMP irradiation.Part I Effects of EMP on Primary Motor Cortex Neurons and MyD88 in SD RatsObjective:To study the effect of EMP on the morphology of primary motor cortex?M1 area?neurons and the expression of MyD88 in neurons in SD rats,and to explore the pathway of EMP damage to central nervous system?CNS?.Method:Forty SD rats were divided into seven groups randomly and they were all males:Control group?10 rats?,EMP irradiated group?5 rats in EMP group for 30 minutes?,EMP irradiated group?5 rats in EMP group for 1 hour?,EMP irradiated group?5 rats in EMP group for 3 hours?,EMP irradiated group?5 rats in EMP group for 6 hours?,EMP irradiated group?24 hours?,EMP irradiated group?5 rats in EMP maze group?;control group?5 rats in EMP irradiated group?.No EMP irradiation is carried out in the spare room.The parameters of EMP irradiation system are field strength 400 kV/m,voltage rise time 3.5 ns,pulse width 14 ns,repetition frequency 1 Hz,pulse 200 p/time,once a day,continuous irradiation for 3 days.The HE staining was intened for observing the morphological changes of M1 neurons in SD rats after EMP irradiation.Western Blot method was used to detect the expression of MyD88 in cortical tissue samples of SD rats after EMP irradiation.Morris water maze method was used to train the control group?5 rats?and EMP group?5 rats?for3 days respectively.The spatial search experiment was conducted to detect the behavioral changes of SD rats after EMP irradiation.Result:HE staining showed that the primary motor cortex?M1?heteromorphic cells in EMP 1 h group increased after irradiation,and the morphology and number of heteromorphic cells changed with the increase of feeding time after irradiation.Western Blot results showed that after EMP irradiation,the expression level of MyD88 in cortical tissue samples of EMP 3 h group and EMP 6 h group increased significantly?P<0.05?;Morris water maze results showed that SD rats in the control group moved longer?P<0.05?.SD rats in the control group moved longer in the inner and middle circles?P<0.05?.SD rats in the EMP group moved longer in the outer circle?P<0.05?.Conclusion:EMP irradiation can cause neuronal damage and degeneration in M1 region of SD rats,and increase the expression of MyD88 in neurons;EMP irradiation can damage the action ability of SD rats.Part II Effects of EMP on hippocampal CA1 neurons,MyD88 and JNK in SD ratsObjective:To study the effect of EMP on neuronal morphology and expression of MyD88and JNK in CA1 area of hippocampus of SD rats,and explore the pathway of EMP damage to central nervous system?CNS?.Method:Thirty SD rats were divided into 6 groups randomly and they were all males.Each group had 5 rats:control group?control group?,EMP irradiation group?30 minutes?,EMP irradiation group?1 hour?,EMP irradiation group?3 hours?,EMP irradiation group?6 hours?,EMP irradiation group?24 hours?,and control group?24 hours?.Rats in the control group were only placed in the irradiation preparation room without electromagnetic radiation.Pulse irradiation.The parameters of EMP irradiation system are field strength 700 kV/m,voltage rise time 3.5 ns,pulse width 14 ns,repetition frequency 1 Hz,pulse 1000p,once a day,continuous irradiation for 3 days.The HE staining was intened for observing the morphological changes of CA1 neurons in hippocampus of SD rats after EMP irradiation.Western Blot method was used to detect the expression of MyD88 and JNK in hippocampal tissue of SD rats after EMP irradiation.Result:HE staining results showed that after EMP irradiation,the number and morphology of hippocampal CA1 cells in EMP 1 h group and EMP 3 h group increased with the increase of feeding time after irradiation.Western Blot results showed that after EMP irradiation,the content of MyD88 in hippocampal tissue protein samples of EMP 3 h group increased significantly?P?27?0.05?;the content of p-JNK in EMP 3 h group began to increase continuously?P?27?0.05?.Conclusion:EMP irradiation can cause hippocampal tissue damage in rats.In addition to up-regulating the expression of MyD88,it can also promote the transformation of JNK to p-JNK,and the duration of the changes is different.This may be the reason for the changes of EMP brain damage over time.PART III Effect of inhibiting JNK pathway on brain injury induced by EMPObjective:To study the effect and mechanism of SP600125 on brain injury induced by EMP irradiation.Method:Eighteen SD rats were divided into 3 groups randomly and they were all males.Each group had 6 rats:EMP irradiation group?EMP?,DMSO group?DMSO?,SP600125group?SP?.The parameters of EMP irradiation system were field strength 700 kV/m,voltage rise time 3.5 ns,pulse width 14 ns,repetition rate 1 Hz,pulse 1 000 p,once a day for 3 days.Feeding continued for 3 hours after the last irradiation.Western Blot method was used to detect the difference of p-JNK expression in hippocampal tissue samples of SD rats after EMP irradiation.The behavioral changes of SD rats in each group after EMP irradiation were detected by water maze method.Result:Western Blot results showed that after EMP irradiation,the expression of p-JNK in SP group was lower than that in the other two groups?P?27?0.05?;water maze results showed that rats in SP group moved longer?P?27?0.05?;rats in EMP group and DMSO group moved longer in the outer ring than those in SP group?P?27?0.05?;rats in SP group moved longer in the inner and middle ring than those in other two groups?P?27?0.05?.Conclusion:SP600125 can alleviate the injury of central nervous system after EMP irradiation,and improve the effect of this injury on learning and motor ability of rats.The mechanism is related to the competitive inhibition of JNK activation by SP600125.
Keywords/Search Tags:Electromagnetic Pulse, Rat, MyD88, JNK, SP600125
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