Effect of hydrogen sulfide on hippocampal endoplasmic reticulum stress during global cerebral ischemia-reperfusion in rats

Objective To evaluate the effect of hydrogen sulfide on hippocampal endoplasmic reticulum stress during global cerebral ischemia-reperfusion (I/R) in rats. Methods Seventy-two pathogen-free healthy male Sprague-Dawley rats, weighing 280-320 g, aged 8-10 weeks, were divided into 3 groups (n=24 each) using a random number table: sham operation group (group Sham), global cerebral I/R group (group I/R) and global cerebral I/R plus sodium hydrosulfide group (group I/R+ NaHS). Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the global cerebral I/R model.Immediately after recovery of spontaneous circulation, sodium hydrosulfide 2.5 mg/kg was intraperitoneally injected in group I/R+ NaHS, and normal saline 5 ml/kg was given in group I/R.The hippocampi were immediately removed at 24 h of reperfusion for determination of the expression of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP) and caspase-12 in hippocampal tissues (by Western blot). At 1, 3 and 7 days of reperfusion, the hippocampal tissues were obtained and stained with haematoxylin and eosin for examination of the pathological changes in hippocampal CA1 region (under a light microscope) and for determination of apoptosis in hippocampal cells (using TUNEL staining), and the apoptosis rate was calculated. Results Compared with group Sham, the apoptosis rate of hippocampal tissues at 1, 3 and 7 days of reperfusion in group I/R and at 3 and 7 days of reperfusion in group I/R+ NaHS were significantly increased, and the expression of GRP78, CHOP and caspase-12 in hippocampal tissues was significantly up-regulated in I/R and I/R+ NaHS groups (P<0.05). Compared with group I/R, the apoptosis rate of hippocampal tissues was significantly decreased, and the expression of GRP78, CHOP and caspase-12 was down-regulated at 1, 3 and 7 days of reperfusion (P<0.05), and the pathological changes were significantly attenuated in group I/R+ NaHS. Conclusion The mechanism by which hydrogen sulfide reduces apoptosis in hippocampal cells is related to inhibition of endoplasmic reticulum stress during global cerebral I/R in rats. Key words: Hydrogen sulfide; Reperfusion injury; Brain; Endoplasmic reticulum Stress