Effect And Significance Of Intervening Autophagy On The M1/M2 Phenotypes Of Microglia In Hippocampus Of Rats With Epilepsy

ObjectiveAfter intervening the level of microglia autophagy in hippocampus of rats with epilepsy,this study was aimed to observe the activation state of the M1/M2 phenotypes and the effect on neurons and epilepsy in order to analysis their correlation and significance.MethodsAccording to the levels of epilepsy,experimental rats kindled by pentylenetetrazole were divided into mild seizure group and major seizure group.Next major seizure group were assigned randomly into three groups:severe seizure group,3MA group and RAPA group.Normal rats were named control group.The behavior of rats were observed and recorded.The HE staining was used to observe the loss of neurons.Immunofluorescence,RT-PCR and western blot were employed to detect the expressions of microglia autophagy(LC3 and CD68),M1 phenotype(iNOS and TNF-a)and M2 phenotype(Argl and TGF-β).ResultsHistological observation showed that neurons went injured on epileptic condition.In mild seizure group,the levels of microglia autophagy increased compared to control group,and the levels of Argl and TGF-β were significantly higher(P<0.05),during there was no change in the levels of iNOS and TNF-a(P>0.05).Compared to mild seizure group,the neurons were further damaged,and the levels of microglia autophagy,CD68,iNOS,Argl,TNF-a and TGF-β were significantly increased(P<0.05).In 3MA group,compared with server control group,the severity of seizure was reduced and the decreased number of neurons was observed(P<0.05).As micriglia autophagy was inhibited,the expressions of iNOS and TNF-α were also reduced(P<0.05),but the expressions of Argl and TGF-βwere significantly higher(P<0.05).In the rapamycin group,seizure was not improved and even caused death,and the number of injured neurons increased markedly compared with server control group(P<0.01).And the levels of micriglia autophagy,iNOS and TNF-a were significantly increased(P<0.05),during the expressions of Argl and TGF-βhad little change(P<0.05).Conclusion1.Epileptic seizures can cause microglia activation,and microglia autophagy exists in the process of epilepsy.2.Improving the autophagy of microglia moderately can promote the differentiation of M2 phenotype in order to protect the neuron at the time of mild epileptic seizures.3.At the time of mild epileptic seizures,adjuvant activity of microglia can promote the expression of M2 in microglia and play a role in protecting neurons.4.Microglia M1 and M2 were significantly increased when epileptic seizures become more serious,and pro-inflammatory effect is greater than anti-inflammatory effect,and then aggravate epileptic seizures.5.As epileptic seizures become more serious,inhibiting microglia autophagy can promote the expression of the M2 phenotype and decrease the differentiation of the M1 phenotype,so that they can protect the neuron and alleviate the symptoms of epileptic seizures.