Neuroprotective effect of ibuprofen on chronic epilepsy and its mechanism in rats models / 中华神经医学杂志

ABSTRACT

Objective:To investigate the neuroprotective effect of ibuprofen, and influence of ibuprofen in hippocampal nod-like receptor protein 3 (NLRP3) inflammatome and its related products in chronic epilepsy rats models.Methods:Thirty male SD rats were randomly divided into 3 groups: control group, pentylenetetrazol (PTZ) group and PTZ+ibuprofen group ( n=10). Rats in the PTZ group were intraperitoneally injected with PTZ (35 mg/kg) once every one d, and rats in the PTZ+ibuprofen group were intraperitoneally injected with ibuprofen (30 mg/kg) once every one d 30 min before PTZ injection; rats in the control group were intraperitoneally injected with the same amount of normal saline every one d. Injection for 15 times was performed. After the last injection, the rats were observed for 10 min, and the latency, seizure level and complete ignition of the rats in each group were recorded. Electroencephalogram (EEG) was used to detect the abnormal brain discharge in rats. Four h after last injection, HE staining and Nissl staining were used to detect the proportion of damaged hippocampal neurons in each group. Immunohistochemical staining was used to detect the absorbance values of NLRP3 inflammasome, caspase-1 and interleukin (IL)-18 positive cells in the hippocampus of rats in each group; Western blotting was used to detect the protein expressions of NLRP3 inflammatome, caspase-1 and interleukin (IL)-18 in the hippocampus of each group. Results:(1) As compared with the PTZ group, rats in the PTZ+ibuprofen group had statistically lower incidence of complete ignition, significantly longer latency and significantly lower seizure level ( P<0.05). EEG showed spikes and high amplitude epileptic wave discharge in rats of the PTZ group; EEG showed low amplitude small spiny wave and slow spiny wave in rats of the PTZ+ibuprofen group. (2) As compared with the control group, the proportion of injured hippocampal neurons significantly increased in the PTZ group and PTZ+ibuprofen group ( P<0.05); and the proportion of injured hippocampal neurons in the PTZ+ibuprofen group signficantly decreased as compared with that in the PTZ group ( P<0.05). (3) As compared with those in the control group, the absorbance values of NLRP3 inflammatome, caspase-1 and IL-18 positive cells, and the protein expressions of NLRP3 inflammatome, caspase-1 and IL-18 in the hippocampus of the PTZ group and PTZ+ibuprofen group were all significantly increased ( P<0.05); as compared with the PTZ group, the the absorbance values of NLRP3 inflammatome, caspase-1 and IL-18 positive cells, and the protein expressions of NLRP3 inflammatome, caspase-1 and IL-18 in the hippocampus in the PTZ+ibuprofen group were all significantly decreased ( P<0.05). Conclusion:Ibuprofen can inhibit the expressions of NLRP3 inflammatome, caspase-1 and IL-18, reduce the intensity of seizures, and play a neuroprotective role.