Regulating effect of endogenous carbon monoxide on brain damage induced by recurrent febrile seizures through GRP78-PERK-eIF2α-CHOP signal pathway / 中华实用儿科临床杂志

ABSTRACT

Objective To observe the effect of endogenous heme oxygenase 1 (HO-1)/carbon monoxide(CO)system on brain damage induced by recurrent febrile seizures (FS) through GRP78-PERK-eIF2α-CHOP signal pathway.Methods Forty-eight SD male rats of 21 days were randomly divided into 4 groupscontrol group,FS group,FS with ZnPP-Ⅸ (FS + ZnPP-Ⅸ) group,and FS with Hemin(FS + Hemin) group,12 rats in each group.Hyperthermia treatment was carried out 10 times,once every 2 days.For group FS + Hemin,Hemin,a CO donor was administered intraperitoneally 0.5 hour before each immersion.For group FS + ZnPP-Ⅸ,ZnPP-Ⅸ,an inhibitor of HO-1 were preconditioned intraperitoneally 0.5 hour before each immersion.The seizure latency,seizure intensity and seizure duration of FS rats were recorded.The content of CO in cortex was measured by using dual wavelength spectropotometey.Neuron apoptosis was detected by using TUNEL.The expressions of GRP78,p-PERK,p-eIF2α and CHOP in cortex were measured by using immunohistochemistry.Results No difference in the seizure latency,seizure intensity and seizure duration in the rats FS + ZnPP-Ⅸ group or the FS + Hemin were recorded,compared with those in the FS group(all P ＞0.05).The content of CO in cortex increased after recurrent FS (P ＜ 0.05).The generation of CO further up-regulated the expressions in FS + Hemin group,while it decreased the expressions in FS + ZnPP-Ⅸ group(all P ＜0.05).Neuronal apoptosis was evident in the FS group.Hemin reduced neuronal apoptosis,up-regulated the expression of GRP78,down-regulated the contents of CHOP,p-PERK and p-eIF2α ;ZnPP-Ⅸ further induced neuronal apoptosis,and down-regulated the expression of GRP78;it aslo up-regulated the expression of CHOP,p-PERK and p-eIF2α.Conclusions Endogenous HO-1/CO system protects the rats from brain damage induced by recurrent FS through endoplasmic GRP78-PERK-eIF2α-CHOP/GADD153 signal pathway.