Expression of nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory corpuscles in epileptic model and the effect of melatonin on its expression

Abstract

Objective To observe the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome in epilepsy model, and to explore the neuroprotective effect of melatonin. Methods SD rats aged 21-30 d were randomly divided into the control group(48 rats), the epilepsy group(48 rats) and the melatonin group(48 rats), and each group was subdivided into 4 subgroups according to the time points of 24 h, 48 h, 72 h, and 7 d, with 12 SD rats in each subgroup.Fluorescence quantitative polymerase chain reaction and immunohistochemical technique were used to analyze the expressions of NLRP3, Caspase-1 and interleukin(IL)-1β in hippocampus areas of rats at different points of time after seizures were induced, and their behavior changes were observed. Results The number of NLRP3-positive cells in the epileptic group increased, and reached the peak at 72 h. At 24 h, 48 h, 72 h, 7 d, the number of NLRP3-positive cells in the epilepsy group(14.20±1.64, 23.60±1.14, 31.20±1.30, 25.40±2.07)was significantly increased compared with those of the melatonin group(10.60±0.89, 17.80±1.48, 24.00±0.71, 20.20±1.92) and the control group(2.60±0.89, 2.40±1.14, 2.40±1.14, 2.40±0.55), and the differences were significant(F=122.977, 375.125, 962.743, 262.916, all P<0.05). The NLRP3 mRNA relative expressions in the epilepsy group (2.57±0.12, 3.34±0.10, 4.84±0.19, 3.55±0.13)were significantly increased compared with those of the melatonin group (2.03±0.08, 2.71±0.08, 4.03±0.14, 2.48±0.18) and the control group(1.07±0.13, 1.08±0.15, 1.08±0.23, 1.07±0.18), and the differences were significant (F=422.386, 1 154.957, 1 132.112, 512.149, all P<0.05); the Caspase-1 mRNA relative expressions in the epilepsy group (2.47±0.07, 3.05±0.15, 4.39±0.18, 3.14±0.11) were significantly increased compared with those of melatonin group(1.85±0.07, 2.49±0.08, 3.60±0.12, 2.15±0.12) and the control group (0.98±0.25, 0.99±0.15, 0.98±0.23, 0.99±0.18), and the differences were significant(F=620.099, 580.796, 1 125.225, 645.082, all P<0.05); the IL-1β mRNA relative expressions in epilepsy group (2.32±0.15, 2.90±0.18, 4.18±0.16, 2.74±0.07) were significantly increased compared with those of the melatonin group (1.78±0.09, 2.35±0.11, 3.24±0.13, 1.78±0.16)and the control group(0.97±0.13, 0.99±0.15, 0.97±0.23, 0.97±0.18), and the differences were significant(F=267.952, 398.767, 1 140.384, 438.962, all P<0.05). Conclusions The NLRP3 inflammasomes are activated in rat hippocampus with epilepsy induced by lithium-pilocarpine.NLRP3 inflammasome mediated inflammatory response probably involved in the pathogenesis of epilepsy.The melatonin may play a neuroprotective role by inhibiting expression of NLRP3 inflammasome. Key words: Pilocarpine; Epilepsy; Nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory corpuscles; Melatonin