The role of endogenous cystathionine beta synthase/hydrogen sulfide and heme oxygenase-1/carbon monoxide in a rat model of global cerebral ischemia-reperfusion / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of endogenous cystathionine beta synthase (CBS)/hydrogen sulfide (H2S) and heme oxygenase-1 (HO-1)/carbon monoxide (CO) during global cerebral ischemia-reperfusion (I/R).Methods Thirty male Wistar rats weighing 180-220g were anesthetized with intraperitoneal (IP) 3% pentobarbiral 40 mg?kg-1. Global cerebral I/R was produced by 4-vessel occlusion. Bilateral vertebral arteries were cauterized and bilateral common carotid arteries were occluded with atraumatic clamps for 20 min. The clamps were then released to allow reperfusion. The animals were randomly divided into 5 groups (n=6 each) group Ⅰ sham operation(C); groupⅡ I/R; in group Ⅲ (Z+I/R),Ⅳ(H+I/R) andⅤ(Z + H + I/R) zinc protoporphyrin (HO-1 inhibitor) 45 ?mol?kg-1 or/and 1 ml of 5 mmol?L-1 hydroxylamine (CBS inhibitor) were given IP 30 min before I/R. The animals were killed at 6h of reperfusion. Brains were removed immediately for determination of H2S, CO, GSH, MDA level and SOD activity and expression of CBS mRNA and HO-1 mRNA in hippocampus and histologic examination with electron microscope. Results H2S, CO, MDA content and CBS mRNA and HO-1 mRNA expression were significantly higher while GSH content and SOD activity were significantly lower in I/R group than in control group (sham operation) . CO content and HO-1 mRNA expression were significantly lower while H2S, GSH content and CBS mRNA expression were significantly higher in Z + I/R group than in I/R group. H2S, GSH content and CBS mRNA expression were significantly lower and CO content and HO-1 mRNA expression were significantly higher in H + I/R group than in I/R group. In Z + H + I/R group H2S, CO, GSH content, SOD activity and expression of HO-1 mRNA and CBS mRNA were significantly decreased whereas MDA content was significantly increased as compared with I/R group. Mitochondria in hippocampal neurons were severely damaged in group Ⅱ-Ⅴ and the damage was worst in group Z + H + I/R. Conclusion CBS/H2S and HO-1/CO systems can protect brain against I/R injury.