Abstract:

Objective To investigate the role and mechanism of endoplasmic reticulum stress protein glu⁃ cose regulatory protein 78（GRP78）in the inflammatory activation of astrocytes after intracerebral hemorrhage （ICH）. Methods ICH was induced by autologous whole blood injection in CD1 mice，and GRP78 targeted inhibitor ha15 was used. Forty⁃two prepared mice were randomly divided into 7 groups：sham operation group and groups of 3，6，12，24，48 and 72 hours after ICH. The expression of GRP78 in the area around hematoma was detected by Western blot. Another group of prepared 36 mice were randomly divided into 3 groups：sham operation，ICH + car⁃ rier（PBS），ICH + ha15. Neurobehavioral tests and brain water content were evaluated at 24 h and 72 h after ICH. At 24 h after ICH，TUNEL method was used to evaluate neuronal apoptosis，and Western blot was performed to analyze the expression of caspase 12 and chop protein，the classical downstream markers of ER stress. Results Compared with the sham operation group，the level of GRP78 in the area around the hematoma began to rise at 3 h after ICH and reached the highest at 24 h（P < 0.05）. At 24 h and 72 h after ICH，compared with ICH + PBS group， the neurological deficit in ICH + HA group was significantly improved（P < 0.05），and the brain edema in the basal ganglia and cortex was significantly reduced（P < 0.05）. After HA treatment，astrocytes，GFAP + GRP78 + cells and TUNEL positive neurons in the area around the hematoma decreased significantly （P < 0.05）. After HA treatment，the expression of caspase 12 and chop protein decreased，and ER stress was significantly inhibited. Conclusion ER stress protein GRP78 participates in nerve injury after ICH by mediating the inflammatory activa⁃ tion of astrocytes. HA15 may have a positive effect on neuronal survival after ICH.

Key words:

endoplasmic reticulum stress, glucose regulatory protein 78, intracerebral hemor? rhage, astrocytes