The Study On The Anti-epileptic Mechanism Of Leptin And Ghrelin

Objective:In this study,patients with seizures and pentetrazol(Penttetrazol PTZ)-induced total tonic-clonic seizures were used to study the effects of leptin and ghrelin on seizures and immune responses(inflammation and The effects of oxidative/antioxidant levels)explore the mechanisms of anti-epilepsy,understand the etiology of seizures,and develop new therapeutic targets.Methods:Animal experiments: 44 Wistar rats of about 200 g were randomly divided into 4 groups(4*11): group A(S): 0.9% sodium chloride solution(Nacl)(10 ml/kg)intraperitoneal injection,group B(S+PTZ)): 0.9% Na Cl(10ml/kg)was injected intraperitoneally,PTZ(65mg/kg),group C(leptin+ PTZ): leptin(4mg/kg)was injected intraperitoneally 30 minutes after injection of Nacl,and PTZ(65mg/kg)was injected 30 minutes after injection of leptin.),group D(Ghrelin + PTZ): Ghrelin(80ug / kg)intraperitoneal injection,injection of Ghrelin 30 min after injection of PTZ(65mg / kg).T he severity and duration of seizures were assessed by observing the seizure behavior of rats.Blood samples from each group were tested for tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),inter leukin-6(IL-6),Catalase(CAT),Thiobarbituric Acid Reactive Substances(TBARS),Malonic Dialdehyde(M DA),and Glutathione(GSH)concentrations.Nissl staining of rat brain tissue was performed to observe the changes of Nissl bodies in hippocampus.Clinical experiment:40 patients with seizures(including generalized seizures and partial seizure s)within 24 hours were selected as epilepsy group,and 40 healthy subjects were selected as norma l control group.Serum leptin and ghrelin levels were measured by ELISA.Result:1.PTZ induced acute epilepsy model success,the incidence of epileptic seizures in the S+PTZ group was 100%.2.4mg/kg leptin prolongs the incubation period of seizures and reduces the incidence and severity of total tonic-clonic hernia.Compared with the S+PTZ group,the leptin+ PTZ group had a full-scale tonic-clonic seizure rate of 60%,and the seizure latency(st1),local seizure(st3),and general seizure(st4)were significantly delayed(P <0.01).The duration was shortened(P < 0.05).3.80μg/kg of ghrelin prolongs the incubation period of seizures and reduces the incidence and severity of total tonic-clonic hernia.When the Ghrelin+ PTZ group was compared with the S+PTZ group,the overall tonic-clonic seizure rate was 25%,and the seizure latency(st1),local seizure(st3),and full seizure(st4)were significantly delayed(P <0.01).Epilepsy The duration of the full episode was shortened and was not statistically significant(P > 0.05).4.Serum inflammation level increased after seizure,S group compared with S+PTZ group,TNF-α,IL-6 significantly decreased levels(P < 0.01)and decreased IL-1β levels(P < 0.05).5.Leptin and Ghrelin intervention can reduce serum inflammatory factor levels in PTZ seizure model.IL-1 levels in leptin+PTZ group were significantly lower than those in S+PTZ group(P <0.05),but TNF-α and IL-1β levels were significantly different.There was no statistically significant decrease(P > 0.05).Compared with the S+PTZ group,the TNF-α and IL-6 levels in the Ghrelin+ PTZ group were significantly different(P < 0.05),and the IL-1β reduction was not significantly different(P > 0.05).6.After serum seizures,serum antioxidant levels decreased,and oxidative levels increased.Compared with S+PTZ group,TBARS and MDA levels were significantly decreased(P <0.01),and GSH and CAT levels were significantly increased(P <0.01).7.Leptin and Ghrelin intervention can reduce the oxidative level of seizure model and increase the level of anti-oxidation.The difference of GSH level between leptin+PTZ group and S+PTZ group is significantly different(P <0.05),and the difference of CAT level is particularly obvious.(P <0.01).Compared with the PTZ+S group,the levels of TBARS and MDA decreased,and the levels of GSH and CAT increased in the Ghrelin+ PTZ group,but there was no statistical significance.8.Loss of neurons in hippocampus after seizures(reduced number of Nissl bodies),S group and S + PTZ group compared with Nissl bodies,Leptin,Ghrelin intervention can protect hippocampal neurons in seizure model,Ghrelin+ Compared with the S + PTZ group,the number of Nissl bodies in the hippocampus of the rats in the PTZ group and the leptin+ PTZ group increased.Conclusions:1.Leptin and ghrelin have anti-epileptic effects in a PTZ-induced epileptic model of general tonic-clonic seizures in rats.2.Epileptic seizures and seizures are associated with inflammation.Leptin and ghrelin may exert anti-epileptic effects by reducing the level of inflammatory mediators in PTZ-induced whole-line tonic-clonic seizure rats.3.Epilepsy and seizures are associated with oxidative stress.Leptin may exert its anti-epileptic effect by increasing the antioxidant level of PTZ-induced pancreatic epileptic model rats.4.Leptin and Ghrelin have neuroprotective effects on hippocampal neurons in rats with PTZ-induced epilepsy induced by generalized tonic-clonic seizures.