The Mechanism Of Tranexamic Acid Ameliorates Intestinal Barrier Injury In A Rat Trauma/Hemorrhagic Shock Model

BACKGROUND: Traumatic hemorrhagic shock is a common cause of death in traumatic patients.Complications,existing scholars have conducted extensive and indepth research on the pathophysiological process and treatment strategies of incision hemorrhagic shock,and proposed methods of allowable hypotension and damage control.After the primary cause of traumatic hemorrhagic shock is effectively controlled,more than half of the remaining patients die of late complications,intestinal mucosal barrier dysfunction is the most critical alternative.Studies have shown that intravenous injection of tranexamic acid(TXA)can effectively protect the intestinal mucosal barrier of wound hemorrhagic shock,but its specific mechanism is still solvable.Our previous studies have shown that in the pathophysiology of sepsis and reducing reperfusion injury.In the process,neutrophil extracellular traps(NETs)are involved in the intestinal barrier function damage.At the same time,there are also literatures that show that a large number of neutrophils infiltrate and infiltrate after penetrating hemorrhagic shock.The pathophysiological role in the process of intestinal barrier injury during traumatic hemorrhagic shock,and the relationship and related mechanism of TXA,net and intestinal barrier injury in traumatic hemorrhagic shock provide new treatment for clinical traumatic hemorrhagic shock intestinal barrier injury The starting point and theoretical basis.METHODS:(1)Establish a rat model of traumatic hemorrhagic shock,and divide the experimental animals into 4 groups: 1)Sham group,2)T / HS group,3)DNase I group,4)TXA group.After the modeling was completed,DNase I group was intravenouslyinjected with DNase I solution to degrade NETs,and TXA group was intravenously injected with TXA.Twenty-four hours later,the blood and terminal ileum specimens of the rats were taken.The serum cytokine levels were measured by ELISA.The HE staining was used to evaluate the pathological damage of intestinal villi.The pathophysiological role of intestinal barrier injury during wound hemorrhagic shock and the related mechanism of tranexamic acid protecting intestinal barrier.(2)Establish a rat model of traumatic hemorrhagic shock,and divide the animals into different TXA defined time groups(TXA 1/3 / 6hr)and different TXA designated dose groups(TXA 5/10/20 mg / kg).24 hours after the modeling was completed,materials were taken(3)neutrophils in healthy volunteers were used for in vitro cell experiments,and the isolated neutrophils were separated from PMA.Or TXA for education,detection of English teacher generation index,ROS generation index,and Western blot detection of protein expression of related pathways,and it is planned to explore TXA related pathways that affect mother tongue production.RESULTS:(1)After T / HS,neutrophils will aggregate and infiltrate and release NETs,resulting in the destruction of internal tight junction proteins;after clearing NETs with DNase I,the expression and interaction of tight junction proteins between each other is significantly increased(2)Compared with the T / HS group,early intravenous injection of TXA(TXA 1hr group)can significantly reduce the generation of NETs and prevent the destruction of tight junction proteins,while the repeated scheduled group(TXA 6hr)compared with the T / HS group,NETs generation level There is no significant difference from intestinal barrier damage.As a result,TXA reduces and inhibits the generation of NETs,protecting the intestinal barrier at a dosage dose,and high-dose(20 mg / kg)TXA treatment shows a better effect than the therapeutic dose(10 mg / kg).However,the results of thrombelastography showed that the R value of the highdose group and(3)in vitro cell experiments showed that the NETs generation index and PMA of the ROS generation level in the TXA group were earlier,and the K value was significantly decreased in the deeper group,indicating that high dose TXA treatment may lead to an increased risk of blood hypercoagulability and thrombosis.Compared with the PMA group,Western Blot showed that the relative expression levels of p-P38/P38 and p-ERK / ERK in the TXA group were significantly lower than those in the PMA group.CONCLUSION:(1)NETs are involved in the pathophysiological process of intestinal barrier injury caused by traumatic hemorrhagic shock.The use of TXA can effectively inhibit the production of NETs to protect the intestinal barrier.(2)Early and high-dose tranexamic acid can protect more effectively.However,high doses are expected to cause a hypercoagulable state of the blood.(3)TXA may transform the generation of NETs through the classic ROS / MAPK transmission.Intestinal barrier.