The Influence Of Erdosteine On The Oxidative Stress And The Level Of IL-1β, IL-6,TNF-α,MMP-2 In Seizure Rats' Hippocampus

ObjectiveTo observe the influence of erdosteine to the activities of superoxide dismutase (SOD), the level of malondialdehyde (MDA) and the level of IL-1β, IL-6, TNF-a, MMP-2 in seizure rats'hippocampus after seizure kindling induced by pentylenetertrazol(PTZ). By this study, investigate the effect of Erdosteine on the pathogenesis of epilepsy, will provide a possible Single-agent multi novel drug targets for the patients'benefit.Method1. Experimental animals and groups:healthy adult male Wistar rats provided by the Yanbian University Medical Experimental Animal Center were randomly divided into 3 groups:PTZ group (n=10), Erdosteine intervention group (n=10) and the control group (n:=10).2. Make seizure kindling model and pre-disposal treatment:Based on the Diehl's seizure kindling process and improve it, make seizure kindling model by PTZ 50 mg/Kg i.p. to PTZ group and erdosteine group, and give erdosteine 50 mg/Kg from stomach to pre-disposal treatment before kindling for erdosteine group.3. Derived and experiment Extract hippocampal neurons rapidly after all model animals'kindling, and detect the activities of SOD and the level of MDA by chemical colorimetric assay. Observe the hippocampal neurons'damages by hematoxylin (HE). Measure the content change of IL-1β, IL-6 and TNF-αin hippocampus by the ELISA double antibody sandwich assay; Observe the distribution of MMP-2 positive cells by Immunohistochemical staining.4. Statistical analysis:The data were represented by x±s test and analyses of variance were carried out by the SPSS 17.0 statistical software.Results1. The results of HE staining:Neurons in hippocampus of the control group were normal microscopically. The PTZ group which have scattered arrangement of hippocampal neurons, reduction in the number, shrunken of Cell body, red staining cytoplasm and condensated nuclear appeared a large number of acidophilic neurons. There were less acidophilic neurons in the hippocampus of erdosteine group. There were significant differences between them (p<0.01).2. MMP-2 positive cells distribute mainly in the hippocampal the pyramidal cells layer and granule cell layer, but also at the molecular level. The staining intensity in normal group and Erdosteine intervention group significantly more decreased than in model group (p<0.05)3. To compare with normal group, the activities of SOD in both PTZ group and erdosteine group were low, and PTZ group was significantly much lower(p<0.01). MDA level in PTZ group was higher than that in normal group(p<0.01), and MDA level in erdosteine group was lower than that in PTZ group(p<0.01).4. In PTZ group and Erdosteine group, the content of IL-10, IL-6 and TNF-a in hippocampus were higher compared with the normal group (p<0.05), but the model group increased more significantly (p<0.01).ConclusionOxidative stress, cytokines diversification and neuronal damage goes with seizure, Erdosteine could inhibit neuronal damage, scavenge free radicals and reduce the role of cytokine production, and may inhibit the activation of MMP-2. it has the effect on brain protection.