Abstract:

Objective To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock， and to clarify its mechanism. Methods A total of 54 healthy adult SD rats were randomly divided into normal group， blast injury complicated with hemorrhagic shock （model） group， and the fluid resuscitation （treatment） group， and there were 18 rats in each group. Among them，10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes. The average survival time（ST）， 24 h and 72 h survival rates of the rats in various groups were observed； the blood pressure （BP）， heart rate （HR）， and respiratory rate （RR） of the rats in various groups were observed； the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， lactate （LAC）， glucose （GLU）， iron ions， glutathione （GSH）， and malondialdehyde （MDA） and the activities of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） in serum of the rats in various groups were detected；Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and heme oxygenase 1 （HO-1） proteins in superior mesenteric artery tissue of the rats in various groups； the pathomorphology of the superior mesenteric artery of the rats in various groups was observed. Results All the rats in normal group survived for 72 h， while the longest ST of the rats in model group did not exceed 9 h. Compared with model group， the ST and 24 h survival rate （SR） of the rats in treatment group were significantly increased （P<0.05）. Compared with normal group， the BP， HR， and RR of the rats in model group were significantly decreased （P<0.01）. Compared with model group， the BP， HR， and RR of the rats in treatment group were significantly increased after fluid resuscitation （P<0.05）. Compared with normal group， the activities of AST and ALT， and the levels of Scr and BUN in serum of the rats in model group were significantly increased （P<0.01）. Compared with model group， the serum levels of LAC and GLU of the rats in treatment group were significantly decreased （P<0.01）. Compared with normal group， the concentration of iron ion， GSH level， MDA level， LDH activity in serum of the rats in model group were significantly increased （P<0.05）； compared with model group， the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased （P<0.01）. Compared with normal group， the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased （P<0.05）；compared with model group， the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased （P<0.05）. Compared with normal group， the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased （P<0.01）； compared with model group， the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased （P<0.01）. The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered， the swelling was significant and the thickness was increased； the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated. The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact， and there was no swelling in the subendothelial matrix； the vascular endothelial cell membrane of the rats in model group was damaged， there were cytoplasmic dissolution and fragmentation， and the swelling of the subendothelial matrix was significant； the swelling of the vascular endothelial cells in treatment group was alleviated. Conclusion Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock， and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

Key words: Blast injury, Hemorrhagic shock, Fluid resuscitation, Ferroptosis, Vascular