Effect of ischemic preconditioning on HSP70 expression and learning/memory after cerebral ischemia-reperfusion in gerbils / 第二军医大学学报

ABSTRACT

Objective: To study the effect of ischemic preconditioning on heat-shock protein 70 (HSP70) expression and the learning,memory functions after forebrain ischemia-reperfusion injury in gerbils. Methods: Gerbils (n=100) were evenly randomized into four groups Sham group, ischemia-reperfusion (I/R) group, ischemia preconditioning (IP) group, and Cycloheximide + IP group (Cycloheximide was administered 30 min before IP). Transient forebrain ischemia-reperfusion model was established by bilateral common carotid artery occlusion according to the method described previously, and ischemia preconditioning model was established as described by Kitagawa. Changes of neuron morphous in hippocampus CA1 region were observed by H-E staining 1, 2, and 3 days after reperfusion. The expression of HSP70 was examined by immunohistochemistry and Western blotting assay. Neuron apoptosis was detected by TUNEL method. The learning/memory functions of gerbils were examined using 4-PTT dry path maze 3, 4, 5, 6, and 7 days after reperfusion. Results: Compared with Sham group, I/R group had significantly decreased survival neurons(P<0. 05), increased neuron apoptosis(P<0. 05), increased expression of HSP70 (P<0. 05), and decreased learning/memory functions(P<0. 05). Compared with I/R group, IP group had significantly increased survival neurons(P<0. 05), decreased neuron apoptosis (P<0. 05), and increased expression of HSP70 (P<0. 05), and improved learning/memory functions (P < 0. 05). However, cycloheximide almost totally abolished the effect of ischemia preconditioning, with the neuron morphology, density, apoptosis, HSP70 expression, and learning/memory functions similar to those of I/R group. Conclusion: Ischemic preconditioning can protect against cerebral ischemia injury and improve the learning/ memory functions after forebrain ischemia-reperfusion damage, which is possibly through promoting HSP70 expression and starting endogenous neuroprotective mechanism, subsequently reinforcing the protective effect against ischemia.