Interaction between endogenous cystathionine synthase/hydrogen sulfide and heme oxygenase-1/carbon monoxide systems during myocardial ischemic-reperfusion: experiment with rats

Abstract

To investigate the interaction between the cystathionine synthase gene (CBS)/hydrogen sulfide (H(2)S) and heme oxygenase-1 (HO-1)/carbon oxide (CO) systems during myocardial ischemia-reperfusion. Twenty-four SD rats were randomly divided into 4 equal groups: ischemia-reperfusion (I/R) group undergoing intraperitoneal injection of normal saline (NS) and then 30 min later undergoing ligation of the left coronary artery (LCA) for 30 min, ischemia-reperfusion + zinc protoporphyrin (I/R + Z) group undergoing intraperitoneal injection of 45 micromol/kg zinc protoporphyrin, a HO-1 inhibitor, 30 min before the ligation of LCA, ischemia-reperfusion + hydroxylamine (I/R + H) group, undergoing intraperitoneal injection of 5 mmol/L hydroxylamine, a CBS inhibitor, 30 min before the ligation of LCA, and ischemia-reperfusion + zinc protoporphyrin + hydroxylamine (I/R + Z + H) group undergoing intraperitoneal injection of zinc protoporphyrin and hydroxylamine 30 min before the ligation of LCA. Another 6 rats underwent sham operation and intraperitoneal injection of NS 30 min before the operation and were used as control (C) group. The rats were killed 2 h after the reperfusion with their hearts taken out. Electron microscope was used to observe the mitochondrial structure. Homogenate of myocardium was prepared to examine the concentrations of H(2)S, CO, glutathione (GSH), malonyldialdehyde (MDA), activity of superoxide dismutase (SOD), and expression level of CBS-mRNA and HO-1-mRNA. The concentration of CO, H(2)S, GSH, and MDA increased, SOD activity decreased, and HO-1-mRNA and CBS-mRNA expression levels increased in Group I/R as compared with Group C (all P < 0.01). In Group I/R + Z the CO level decreased, H(2)S and GSH levels increased, and HO-1-mRNA expression level decreased, but CBS-mRNA expression level increased as compared with Group I/R (all P < 0.05). In Group I/R + H the H(2)S and GSH levels decreased, CO level increased, and HO-1-mRNA expression level increased and CBS-mRNA expression level decreased as compared with Group I/R (all P < 0.05). In Group I/R + Z + H the H(2)S, CO, GSH, and SOD levels decreased, MDA level increased, and HO-1-mRNA and CBS-mRNA expression levels decreased as compared with Group I/R (all P < 0.05). Electron microscopy found that mitochondrial structure was destroyed in the Groups I/R, I/R + Z, I/R + H, and most seriously in Group I/R + Z + H. Both CBS/H(2)S and HO-1/CO systems play a protective role in myocardial ischemia-reperfusion and they interact on each other.