Effects of cerebral ischemia and postconditioning on signaling molecules PERK and GRP78 in hippocampus tissue of tree shrew during endoplas-mic reticulum stress / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM:To investigate the effects of cerebral ischemia and postconditioning on protein kinase R-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78) in the hippocampus tissue of tree shrew during endoplasmic reticulum stress and the mechanism of post-conditioning protecting the brain from damage.METH-ODS:The focal cerebral ischemic model was duplicated by photochemical reaction in tree shrew and the postconditioning was induced by alternatively occluding and opening the carotid artery of ischemic side for 3 cycles (5 min each cycle) at 3.5 h after ischemia.The damage and ultrastructural changes of the hippocampal neurons were observed by HE staining. The expression of PERK and GRP78 at mRNA and protein levels in the hippocampal tissue at different time points after cer-ebral ischemia and postconditioning was determined by RT-PCR, immunohistochemistry and Western blot.RESULTS:The injuries of hippocampal neurons were aggravated with prolonged cerebral ischemia, which was most severe at 24 h after ischemia while the postconditioning alleviated these damages correspondingly.The expression of PERK at mRNA and pro-tein levels was upregulated at 4 h, 24 h and 72 h after ischemia (P lated the expressions of GRP78 at IP24 h group (P<0.05).CONCLUSION:The focal thrombotic cerebral ischemia ac-tivates the endoplasmic reticulum stress in ischemic hippocampus of tree shrews, leading to the changes in mRNA and pro-tein expression of PERK in the PERK/eIF2αsignal transduction pathway.The postconditioning treatment alleviates endo-plasmic reticulum stress and neuronal damages by downregulating PERK and upregulating GRP78, thereby protecting the brain from injury.