| The massive blood loss caused by war trauma or severe injury usually induces in lacking and redistributing of effective circulating blood volume. The neuroendocrine response to this injury and hemorrhagic shock attempts to maintain perfusion to the heart and brain at the expense of organs such as the gut. This results in lesions of the intestinal mucosa. After resuscitation, the repercussion of intestine is the second hit of the intestinal barrier. Disruption of intestinal epithelial barrier integrity in intestinal ischemia/repercussion(I/R) injury is a primary mechanism for bacterial translocation resulting in SIRS, lethal sepsis and multiple organ failure, which will lead to death.n-3PUFAs, an important active ingredients in fish oil, is commonly used as immune nutrients in clinical. A large number researches have confirmed that it has the protective effects on tight junctions of the intestinal mucosal, and attenuate the systemic inflammatory response and change its signal transduction pathways by replacing the arachidonic acid(AA) contained in membrane phospholipid bilayer in a short time. Meanwhile, n-3PUFAs can blunt the neuroendocrine response of organisms to the endotoxin. In our study, we evaluate the protection of N-3PUFAs for gut barrier and hemodynamic stabilization. Part lFish Oil improves Hemodynamic Stabilization and Inflammation after Resuscitation in a Rat Model of Hemorrhagic ShockBackground:Hemorrhagic shock followed by resuscitation stimulates an inflammatory response and hemodynamic instability. This study tests the hypothesis that treatment with fish oil will attenuate inflammatory responses and stabilize hemodynamics.Methods:Male SD rats (n=72;250-300g) were randomly divided into6groups: SHAM, hemorrhagic shock (HS), hemorrhagic shock/resuscitation (HS/R), ω-6, ω-3and ω-3treatment group. Shock was induced, and a mean arterial pressure (MAP) was maintained at35to40mmHg for60minutes. Resuscitation was carried out by returning half of the shed blood and Ringer’s lactate solution to the animals. In ω-6group and co-3group, Intralipid or fish oil (0.2g/Kg) was infused through caudal vena at30minutes after shock. And fish oil was infused with resuscitation in co-3treatment group. Half of each group was killed at30minutes and at4hours after resuscitation. Then several kinds of inflammation and oxidative stress indicators such as IL-6, MPO and GSH were tested.Result:ω-3group and co-3treatment group required less resuscitative fluid at the recovery periods from hemorrhagic shock than HS/R group(p<0.001) and had higher urinary output than HS, HS/R and ω-6groups(p<0.001). After resuscitation, the MAP of HS/R group and ω-6group markedly declined than co-3group and ω-3treatment group (p<0.001). The inflammatory indexes of co-3group and ω-3treatment group were lower than HS, HS/R and ω-6group and same as sham group. But the level of endotoxin in FO group was significantly higher than sham group at4hours.Conclusion:Fish oil treatment before or during fluid resuscitation showed a beneficial effect to the hemodynamic stabilization and inflammation reduction in HS/R rat model. Part2The study of n-3PUFAs protecting the gut barrier in rat HS/R modelBackground:n-3PUFAs, as a pharmaconutrients, have been demonstrated in vitro that it could prevent the intestinal tight junction(TJ) from the ischemia/re-perfusion injury and the inflammatory reaction injury. The purpose of this study was to evaluate the protection of n-3PUFAs for the intestinal TJ in the rat model of hemorrhagic shock followed by resuscitation.Methods:Male SD rats (n=72;250～300g) were randomly divided into6groups: SHAM, hemorrhagic shock (HS), hemorrhagic shock/resuscitation (HS/R), ω-6, co-3and ω-3treatment group. Shock was induced, and a mean arterial pressure (MAP) was maintained at35to40mmHg for60minutes. Resuscitation was carried out by returning half of the shed blood and Ringer’s lactate solution to the animals. In ω-6group and ω-3group, Intralipid or fish oil (0.2g/Kg) was infused through caudal vena at30minutes after shock. And fish oil was infused with resuscitation in ω-3treatment group.Half of each group was killed at30minutes and4hours after resuscitation. Blood sample was collected and serum was separated by centrifugation and stored at-80℃for analysis. The intestine sample was collected for the examination of histology, scanning electron microscopy(SEM) and laser scanning confocal microscope(LSCM).Result:There is no difference between ω-3group, ω-3treatment group and sham group in Chiu’s score, but the other three groups have higher scores than they did. Compared with HS, HSR and ω-6group, ω-3group and co-3treatment group showed most intact in intestinal mucoscal villi and tight junction through HE, SEM and LSCM. The levels of bowel tissue IL-6and TNF-a in co-3group and ω-3treatment group were significantly lower than HS group and HSR group, and were no different with sham group. At30min, the levels of serum endotoxin were dramatically higher in HS group, HSR group and ω-6groups when compared with ω-3group, ω-3treatment group and sham group. However, to4hours, the level of endotoxin in ω-3group rised and was greater than sham and HS group. Conclusion:Fish oil treatment before and during fluid resuscitation showed a beneficial effect to the intestinal TJ in HS/R rat model. |
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