Study On The Expression Of GRP78 And GADD153 After Cerebral Ischemia Reperfusion In Rats

Objective:Neuronal apoptosis is one of the important reasons of reperfusion injury, but its mechanism remains to be investigate further more. Endoplasmic reticulum stress is a cytoprotective response to multiple stresses, however, prolonged and/or excess endoplasmic reticulum stress can eventually trigger apoptosis. The experiment was performed to define the expression of GRP78 and GADD153 and the relationship between endoplasmic reticulum stress and neuronal apoptosis in rats after cerebral ischemia reperfusion.Materials and methods:72 adult male SD rats were included as research subjects. They were divided into Middle Cerebral Artery Occlusion (MCAO) groups and sham surgery group randomly. Focal cerebral ischemia was induced by MCAO using an intraluminal thread model. Reperfusion was accomplished by withdrawing the suture. The MCAO groups were divided into five groups: 2h, 6h, 12h, 24h and 48h. The experiment was finished as following steps:â‘ Apoptosis was detected by terminal deoxynucleotidyl transferase mediated nick end labeling(TUNEL);â‘¡The expression of GRP78 and GADD153 mRNA was detected by RT-PCR;â‘¢Immunohistochemistry and Western-blot were applied to evaluate the expression of GRP78 and GADD153 protein.Results:â‘ Apoptosis occurred in all MCAO groups, the percentage of TUNEL positive cells in 24h reperfusion group was the highest among all of the group(sP<0.01);â‘¡The expression of GRP78 increased since 2h after ischemia reperfusion and peaked at 12h after reperfusion(P<0.05), then decreased successfully;â‘¢GADD153 increased significantly at 6h after reperfusion and peaked at 24h(P<0.01). The changing trend of GADD153 was consistent with apoptosis.Conclusions:Cerebral ischemia reperfusion induces endoplasmic reticulum stress response. While the overexpression of GADD153 seems to contribute to neuronal apoptosis, GRP78 may be involved in neuroprotective process.