| Cardiac arrest(CA)is a common clinical emergency,which means that the sudden stop of the heart,or the heart cannot pump blood effectively,with the interruption of systemic circulation,respiratory arrest,and loss of consciousness.At present,It is accepted that 4 minutes is the prime time for rescue.Thus,timely and effective cardiopulmonary resuscitation is extremely significant.In non-cardiac cardiac arrest,the great account of cardiac arrest is caused by airway obstruction asphyxiated is in children and the elderly.Because of the lack of professional training in family members,it often cannot operated timely and effectively,causeing serious consequences,Even if the rescue is successful,severe neurological sequelae are often caused by the brain injury after resuscitation,the patients and their families often suffer heavy burden because of the brain injury.In addition,except chest compressions in time how to reduce brain injury after cardiopulmonary resuscitation,which is always a difficult problem for clinical medicine for brain resuscitation.The only proven mild-hypothermia therapy is currently effective.In recent years,it has been found that ischemic postconditioning has a very good protective effect on ischemia reperfusion injury.It has been found in clinical practice that inflation and deflation of the angioplasty balloon after reopening of the coronary artery can protect ischemic myocardium.In the past,through animal experiments,it was also found that ischemic postconditioning has protective effects on cerebral ischemia reperfusion injury.Remote ischemic postconditioning(RIPost)is one of ischemic postconditioning,that involves a series of brief mechanical occlusions and reperfusions of the limbs after ischemia reperfusion.Because it is implemented after ischemia,and is simple and easy to perform,it is an effective measure to reduce the brain injury caused by sudden cardiac arrest,especially for patients with out-of-hospital cardiac arrest,and further advanced life support earlier may reduce the brain injury after resuscitation.Remote ischemic postconditioning is of great clinical value for the protection of brain injury after cardiopulmonary resuscitation.Previous animal studies have found that remote ischemia postconditioning can protect the mouse brain from cerebral ischemia reperfusion injury by up-regulating the expressions of Nrf2,HO-1 and NQO-1 in mice.Remote ischemia postconditioning can reduce the inflammatory response after ischemia reperfusion,and further alleviate the global cerebral ischemia reperfusion injury caused by asphyxial cardiac arrest.Nrf2 is a promising therapeutic target for cerebral ischemia/reperfusion injury.Its activity can be enhanced by health food,many Chinese herbs and other factors,and it is a key regulator of endogenous protection mechanism of the body,which can greatly enhance the Anti-inflammatory,anti-oxidative stress and other abilities.In this study,the model of global cerebral ischemia reperfusion injury induced by asphyxial cardiac arrest(ACA)was used to observe the effects of remote ischemic postconditioning after restoration of spontaneous circulation(ROSC)on hippocampal morphology,the expression of Nrf2 and HO-1 proteins in the hippocampal tissues,and serum neuron specific enolase(NSE)concentration.Furthermore,PI3 K antagonist LY294002 was used to reveal the role of PI3K/Akt/Nrf2 signaling pathway in the neuroprotective effects in RIPost Alleviating Rat brain Injury induced by cardiopulmonary resuscitation(CPR).Experiment I The Expression of Nrf2/HO-1 in Remote Ischemic Post-conditioning Alleviating Rat brain Injury induced by Cardiopulmonary ResuscitationObjective: To investigate the expression alternation and the effect of Nrf2 and HO-1 in remote ischemic post-conditioning alleviating rat brain injury induced by cardiopulmonary resuscitation.Method(s): A total of 45 adult male SD rats were randomly divided in to Sham-operation group(Group Sham),asphyxial cardiac arrest resuscitation group(Group Control)and remote ischemic post-conditioning group(Group RIPost),with 15 cases in each group.The rats in Group Control were induced by 8-min asphyxiation and resuscitated with a standardized method,The remote ischemic post-conditioning models were established in Group RIPost on the basis of the Group Control.At the 24 th hour after ROSC,pathomorphological changes in brain tissues were detected by HE staining,and the contents of Neuron specific enolase(NSE)in serum were assessed by ELISA,the protein and m RNA expression of Nrf2,HO-1 in rat brain tissues were detected by Western blotting,immunohistochemistry and real-time(RT)PCR.Result(s): Compared with Group Sham,acute ischemic changes were found in Group Control,which hippocampal neurons were obviously damaged,and NSE concentration in serum was increased significantly(P< 0.05);while the pathological changes and serum NSE concentration in Group RIPost were milder than those in Group Control(P< 0.05);the protein expressions of nuclear Nrf2 and HO-1 in Group Control and Group RIPost were higher than those in Group Sham,and the expressions in Group RIPost were higher than those in Group Control(all P< 0.05).In addition,RT-PCR analysis showed that there were no significant differences in Nrf2 m RNA levels in three groups(P>0.05),but HO-1m RNA expression in Group RIPost was significantly higher than that in Group Control (P< 0.05).Conclusion(s): Remote ischemia post-conditioning can relieve brain injury induced by cardiopulmonary resuscitation,and the neuroprotective mechanism of RIPost may be related with the Nrf2/HO-1 signaling pathway.Experiment Ⅱ The role of PI3K/Akt/Nrf2 in the neuroprotective effects induced by RIPost in a rat model of brain injury after cardiopulmonary resuscitationObjective: To investigate whether the PI3K/Akt/Nrf2 signaling pathway is involved in the neuroprotective effects induced by RIPost in a rat model of ACA.Methods: Forty adult male SD rats were randomly devided into six groups : sham operation group(Sham group,n=5),asphyxial cardiac arrest resuscitation group(Control group,n=7),remote ischemic postconditioning group(RIPost group,n=7),remote ischemic postconditioning with the PI3 K inhibitor LY294002 group(LY294002+ RIPost group,n=7),LY294002 group(n=7)and DMSO(n=7)group.Sham group rats were only treated with femoral arteriovenous puncture and tracheal intubation.The Control Group was treated with 8-min asphyxiation and resuscitated with a standardized method.The RIPost Group were treated with remote ischemic post-conditioning immediately after ROSC.In the LY294002+ RIPost group,the PI3K-specific inhibitor LY294002 1.8 mg/kg was intraperitoneally administered 30 min before modeling.After the model was established,the rats were treated with remote ischemic post-conditioning immediately after ROSC.LY294002 group: LY294002 1.8 mg/kg was given intraperitoneally 30 min before modeling,and no post-treatment of remote ischemia was given after CPR.DMSO group:Intraperitoneal injection of pure diluted DMSO 30 min before modeling,and then a model of asphyxial cardiopulmonary resuscitation was established.At the 24 th hour after,the contents of IL-1β,TNF-α and IL-6 in cortical were assessed by ELISA,the expression of p-Akt,Nrf2,HO-1 in rat brain tissues were detected by Western blotting.Result(s): Compared with Sham Group,the concentrations of IL-1β,TNF-α and IL-6 in cortical brain tissues of control group,RIPost group,LY294002+ RIPost group,LY294002 group and DMSO group were increased(P< 0.05);Compared with the Control group,the concentrations of IL-1β,TNF-α and IL-6 in the cerebral cortex of the RIPost group were decreased(P< 0.05);However,there were no significant decreases in IL-1β,TNF-α and IL-6 in cortical brain tissue after the administration of antagonist,and the differences were not statistically significant(P< 0.05);After CA,I/R up-regulated the expression of p-Akt,nuclear Nrf2 and HO-1,RIPost significantly increased the protein expressions of p-Akt,nuclear Nrf2 and HO-1 when compared with levels in the Sham and Control groups.While the protein expressions of p-Akt,nuclear Nrf2 and HO-1 in LY294002+ RIPost group were milder than those in RIPost group,the difference between the two groups was statistically significant(P< 0.05).Conclusion: PI3K/Akt/Nrf2 could be involved in the neuroprotective effects induced by RIPost in the rat model of ACA through up-regulating the protein expression of p-Akt,nuclear Nrf2 and HO-1. |
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