Effects of carbon monoxide-releasing molecule-2 on intestinal barrier function in cardiopulmonary resuscitation rats / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effects of carbon monoxide-releasing molecule-2 (CORM-2) on intestinal barrier injury in cardiopulmonary resuscitation (CPR) rats.METHODS:The model of intestinal ischemia-reperfusion injury after cardiac arrest (CA) -CPR was established by intravenous injection of potassium chloride (4℃) combined with asphyxiation for 4 min, followed by artificial chest compression for 3 min.The SD rats (n=32) were randomly divided into 4 groupssham group, CPR group, CORM-2 group and inactivated CORM-2 (i CORM-2) group, with 8 rats in each group.The rats in sham group were instrumented with catheter without experiencing cardiac arrest or CPR.The rats in other groups were inserted with the catheters and underwent CA-CPR.In CORM-2 group and i CORM-2 group, the rats were given CORM-2 at 4 mg/kg and i CORM-2 at 4 mg/kg by intraperitoneal injection at 12 h before CA-CPR.In sham group and CPR group, the rats were administrated with an equivalent volume of vehicle.The hemodynamic data were monitored for 4 h after resuscitation (or catheterization) in each group.The ileum tissues and blood samples were harvested at 4 h after resuscitation (or catheterization).Histopathological changes and ultrastructure of the ileum were observed by HE staining and transmission electron microscopy.The levels of intestinal fatty acid binding protein (I-FABP) in the blood was measured by ELISA.The protein expression of claudin-3, occludin, ZO-1 and proinflammatory factor tumor necrosis factor-α (TNF-α) in the ileum tissues was determined by Western blot.RESULTS:No significant difference of mean arterial pressure (MAP) immediately after catheterization between sham group and resuscitation groups was observed.In CPR group, CORM-2 group and i CORM-2 group, the MAP at each time point after resuscitation was obviously lower than that immediately after catheterization and this phenomenon continued until 4 h after resuscitation (P<0.05).The MAP at each time point after resuscitation in all resuscitation groups was prominently lower than that at the same time points in sham group (P<0.05).The MAP at each time point after resuscitation in CORM-2 group was higher than that in CPR group and i CORM-2 group (P<0.05).The histopathological changes and ultrastructural damage of ileum mucosa in CPR group were obvious.In CORM-2 group, the histopathological changes and ultrastructural integrity of ileum mucosa were significantly better than those in other resuscitation groups.Compared with sham group, the level of I-FABP in CPR group and i CORM-2 group was significantly increased (P<0.05).The level of I-FABP in CORM-2 group showed no statistically significant difference as compared with sham group.The level of I-FABP in CORM-2 group was notably lower than that in CPR group and i CORM-2 group (P<0.05).Compared with sham group, the expression of claudin-3, occludin and ZO-1 in ileum tissues was decreased in CPR group and i CORM-2 group (P<0.05) , but in CORM-2 group, only the expression of claudin-3 and ZO-1 were decreased (P<0.05).The levels of the above proteins in CORM-2 group were higher than those in CPR group and i CORM-2 group (P<0.05).Compared with sham group, the expression of TNF-αin ileum tissues was increased in CPR group and i CORM-2 group (P<0.05) , and the level of TNF-αin CORM-2 group showed no statistically significant difference as compared with sham group.The protein level of TNF-αin CORM-2 group was lower than that in CPR group and i CORM-2 group (P<0.05).CONCLUSION:Cardiac arrest-cardiopulmonary resuscitation causes severe damage of intestinal mechanical barrier in rats.CORM-2 may protect the intestinal barrier integrity in cardiopulmonary resuscitation rats by up-regulating the expression of tight junction proteins in the intestinal epithelium.