The Influence Of Dexmedetomidine On Oxidative Stress And Cytokines Release During Postpartum Hemorrhage

Background and ObjectiveMultiple organ dysfunction syndrome （MODS) refers to suffer from severewounds, shock and infection, when patients with primary non-organ dysfunction,meanwhile or in a short time,dysfunction have appeared more than two organsystems,so that the body must rely on clinical intervention to maintain the stability ofthe environment. At present, free radical damage and cytokines, inflammatorycytokines induced uncontrolled SIRS is the main mechanism of MODS. Althoughearly fluid resuscitation, antibiotic intervention, enteral nutrition, mechanicalventilation and important organ supportive treatment had achieved remarkableprogress, but the death statistics has not changed. Postpartum hemorrhage is acommon and serious obstetric complications, which is the first cause of maternalmortality in our country. Postpartum hemorrhage can cause hemorrhagic shock, whichlead to tissue and organ ischemia and hypoxia, even lead to multiple organ failure.Postpartum hemorrhage is one of the main causes of maternal multiple organdysfunction syndrome. Thus, it is our urgently to solve problems, to improve thetreatment level in multiple organ dysfunction syndrome induced by postpartumhemorrhage, to find effective solutions to minimize maternal mortality.With the study of the pathogenesis of postpartum bleeding-induced MODS,abnormal intestinal immune function plays an important role in the pathogenesis of MODS. A large number of pro-inflammatory cytokines and inflammatory mediatorsreleased from the parenteral into blood circulation, the systemic response activatedexcessively in patient body, a large number of cytokines medium and cell factors arereleased,which can cause SIRS. SIRS is due to a large number of inflammatory cellsactivated and release large amounts of inflammatory mediators caused uncontrolledinflammatory response; Plasma TNF-α, IL-8and IL-6and other pro-inflammatorycytokines release significantly increased，and anti-inflammatory cytokine IL-13, IL-11,IL-10and IL-4, also increased significantly; a large number of endothelial cells andleukocyte expressing adhesion molecules, leading to uncontrolled inflammation,cytokine production cascade effect, tissue destruction and damage, eventually leadingto the occurrence of MODS. In addition, when intestinal ischemia, hypoxia, intestinalmucosa epithelial cells are rich in a large number of xanthine dehydrogenase intoxanthine oxidase,when microcirculation perfusion, xanthine oxidase catalysis oxygenmolecules to form a large number of oxygen free radicals, oxygen radicals damagecells causing organ dysfunction.The pathogenesis of postpartum MODS are still not clear, the clinical patient’scondition is not the same as each other; specimens collected are largely limited atpresent, so large-scale clinical studies are difficult. But there is no mature postpartumhemorrhage animal model of MODS. Most of the existing models of MODS based onclinical etiology or owing to multiple compound of injury. In this study, according tothe pathogenesis of MODS inflammation is out of control theory, theory of ischemiareperfusion, toxin theory of displacement, stress gene theory, etc. We establish amodel of MODS owing to uncontrolled hemorrhagic shock and blocked the superiormesenteric artery, to simulate the animal model of postpartum bleeding-inducedMODS.Dexmedetomidine is a highly selective α2receptor agonist, which has ananalgesic, sedative effect, and no respiratory depression, can inhibit norepinephrinerelease, and inhibit the production of tumor necrosis factor, with a powerfulanti-inflammatory effect, and is widely used in anesthesia and ICU sedation. α2 receptors are widely found in the central and peripheral nervous system, and vitalorgans, including the liver, pancreas, kidneys, blood vessels and platelets.Experimental studies have demonstrated that DEX has a protective effect againstischemia-reperfusion injury in several organs, including heart brain, kidneys, and liver,which is thought to be because of the antioxidant and anti-inflammatory properties ofthe compound. in the anti-inflammatory and antioxidant, We evaluated the effects ofDEX during postpartum bleeding-induced MODS in rats, which provide the referencefor clinical treatment.MethodsThirty six postpartum rats weighing230±40g(SPF) were randomly assignedinto four groups of9rats each: including control group (S), model group (S+C),low-dose dexmedetomidine group (S+C+D25), high-dose dexmedetomidine group(S+C+D50). control group(S): Only for anesthesia,catheters placed in femoral arteryand femoral vein; model group(S+C): rats with bleeding-induced hypotension forsixty minutes and clamping of the superior mesenteric artery for forty minutes;low-dose dexmedetomidine group(S+C+D25): DEX (25μg/kg) was injected into theperitoneal cavity30min before bloodletting. Procedures following this step were thesame as those of group S+C; high-dose dexmedetomidine group(S+C+D50): DEX (50μg/kg) was injected into the peritoneal cavity30min before bloodletting. Proceduresfollowing this step were the same as those of group S+C. All of the rats wereeuthanized after24hours at the end of experiment. The right lung and small intestinewere removed and stored at-80℃until biochemical analysis. Malondialdehyde(MDA), nitric oxide(NO),superoxide dismutase (SOD),glutathione (GSH),catalase(CAT),tumor necrosis factor α and interleukin-6（IL-6）levels were measured.Results1. Dexmedetomidine affect oxidative stress indicatorsThe tissue levels of oxidative stress markers MDA，NO in group S+C werehigher than those in group S (p<0.05). The tissue levels of oxidative stress markersSOD,GSH and CAT in group S+C were lower than those in group S (p<0.05). The tissue levels of oxidative stress markers MDA,NO in group S+C+D25and S+C+D50were significantly lower than those in group S+C (p<0.05). The tissue levels ofoxidative stress markers SOD,GSH and CAT in group S+C+D25and S+C+D50werehigher than those in group S+C (p<0.05).2. Dexmedetomidine affect pro-inflammatory cytokinesThe tissue levels of pro-inflammatory cytokines TNF-and IL-6in group S+Cwere higher than those in group S (p<0.05). The tissue levels of pro-inflammatorycytokines TNF-and IL-6in group S+C+D25and S+C+D50were higher than thosein group S+C (p<0.05).Conclusions1. Dexmedetomidine was injected into the peritoneal cavity，which can reduceoxidative stress injury of lung and intestine, that is due to postpartumbleeding-induced multiple organ dysfunction syndrome.2. Dexmedetomidine was injected into the peritoneal cavity，which can inhibitpro-inflammatory cytokines TNF-and IL-6of lung and intestine, which have acertain anti-inflammatory effects.