Role of endoplasmic reticulum stress in rats after ischemia-reperfusion brain injury / 中华神经医学杂志

ABSTRACT

Objective To observe the dynamic changes of growth arrest and DNA damage inducible gene 153 (GADD 153) and caspase-12 expressions in the brain of rats after ischemia-reperfusion,and explore the role of endoplasmic reticulum stress in ischemia-reperfusion brain injury.Methods Forty-two rats were randomly divided into control group (n=3),sham-operated group (n=3) and ischemia-reperfusion group (n=36); the rats of ischemia-reperfusion group were randomly sub-divided into groups of 2 h occlusion and 6,12,24,72 h reperfusion (n=9).Modified Longa intraluminal thread method was adopted to establish the middle cerebral artery occlusion-reperfusion models.Expression changes of GADD 153 and caspase-12 at different time points were detected by immunohistochemistry,double-label immunofluorescence and Western blotting.Results Immunohistochemistry and Western blotting showed that the expressions of GADD153 and caspase-12 in the control group and sham-operated group was negative; the GADD 153 expression increased in group of 6 h reperfusion,and that in group of 72 h reperfusion was significantly higher than that in group of 6 h reperfusion (P＜0.05);the caspase-12 expression increased in group of 6 h reperfusion,enjoyed the highest level in group of 24 h reperfusion which had significant difference as compared with that in group of 6 h reperfusion (P＜0.05),and still maintained at a high level in group of 72 h repefusion.Double immunofluorescence staining showed that GADD153 and caspase-12 double-positive cells could be seen in group of 6 h reperfusion;that at groups of 12 and 24 h reperfusion significantly increased as compared with that in group of 6 h reperfusion (P＜0.05); the number of caspase-12 single-positive cells reduced,that of GADD153 single-positive cells was still large,and the number of double-positive cells reduced.Conclusion The expression changes of GADD153 and caspase-12 are time dependent,indicating that endoplasmic reticulum stress involve in the pathological process of ischemia-reperfusion brain injury.