| Cardiac arrest(cardiac arrest,CA)is one of the most important causes of cerebral ischemia and reperfusion injury.At present,it has become one of the most dangerous and urgent diseases.Cardiopulmonary resuscitation(cardiopulmonary resuscitation,CPR)is the main method of treatment for cardiac arrest today.Early CPR is essential to save the lives of cardiac arrest patients.However,when the blood reperfuses various organs after CPR,it will cause different degrees of organ damage,which is called ischemia and reperfusion injury,which can involve the heart,kidney,liver,brain and so on.Among them,the brain need real-time blood supply,and its own reserve reserves,so sufficient blood supply is crucial to the brain,when cardiac arrest,blood supply interruption,the brain by the first blow,after positive rescue of cardiopulmonary resuscitation,the occurrence of ischemia reperfusion injury is equal to the second blow,the consequences are very serious,at the same time,the brain is the most important central nervous system,the whole body organs play a core role.Therefore,it is particularly important to protect the brain and reduce the ischemia and reperfusion injury of the brain.NMN is a nucleotide,well known for its role as an intermediate in the biosynthesis of nicotinamide adenine dinucleotide(NAD~+).It has been studied to reduce its role in ischemia and reperfusion,but there are few studies in cerebral ischemia and reperfusion,and the mechanism is not complete.This study first counted the data of cardiac arrest patients admitted in 2019-2020 in a third-class hospital in Jilin province to analyze the risk factors that trigger cardiac arrest.By analyzing the transcriptome data of the rat cerebral ischemia-reperfusion model,the changes of gene expression during cerebral ischemia-reperfusion were clarified,and then the molecular mechanism of triggering ischemia-reperfusion injury was explored.Finally,NMN was used to treat cerebral ischemia-reperfusion rats to observe their therapeutic effect and explore the mechanism.The study aims to explore the occurrence of ischemia and reperfusion injury,clarify the therapeutic effect and mechanism of NMN on ischemia reperfusion injury,and provide theoretical support for reducing the injury in patients with ischemia and reperfusion injection.The main findings are as follows:1.The information was collected on cardiac arrest patients admitted in a third-class hospital in Jilin province,and the relationship between age,gender,smoking history,drinking history,the main factors of cardiac arrest,as well as CPR and survival of patients was statistically analyzed.The results showed that:(1)patients with cardiac arrest were more concentrated over 60 years old,accounting for63.87%of the total number,and the male/female ratio was about 1.5:1;(2)The juvenile cardiac arrest factors were mainly related to lung infection(51.85%)and respiratory failure(37.04%)and there are 8 cases of congenital heart disease patients.The main causes of cardiac arrest in 19-44 age group were acid-base imbalance/electrolyte disturbance(44.33%)and pulmonary infection(36.79%),Respiratory failure(22.64%)and renal insufficiency(21.69%).In addition to acid-base imbalance/electrolyte disturbance in 45-59 years(34.89%),pulmonary infection(31.48%),hypertension(28.51%)caused cardiac arrest(28.5%),acute stroke(20.85),and malignancy(15.74%).The main causes of cardiac arrest in age groups aged 60-74 years were pulmonary infection(43.52%),hypertension(40.92%),coronary heart disease(25.36%),and diabetes mellitus(24.74%).The main causes of cardiac arrest were pulmonary infection(56.63%),hypertension(52.76%),acid-base imbalance/electrolyte disorder(43.92%)and coronary heart disease(41.16%),and in15.19%of patients with congestive heart failure.(3)The prognosis of the patients was related to CPR,age and cardiac arrest factors(P<0.05).The results show that the vast majority of patients with CA is the elderly,different ages of cardiac arrest,minor cardiac arrest factors mainly for lung infection,respiratory failure,and the factors of congenital heart disease,middle-aged patients,the frequency of elderly heart disease and hypertension.The prognosis of patients is closely related to the absence of CPR,and the factors of age and cardiac arrest are also important factors affecting the prognosis.2.By analyzing the transcriptome data of cerebral ischemia-reperfusion rat model,differentially expressed genes were screened out between the control group and the ischemia-reperfusion group,and pathway enrichment analysis and key gene screening were performed.The results showed that:(1)gene expression changed significantly after cerebral ischemia-reperfusion,and more genes were up-regulated;(2)After cerebral ischemia-reperfusion,genes were mainly enriched in TNF signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,cytokine-cytokine receptor interaction and other signaling pathways.(3)Myc,Stat3,Cxcl10,Atf3,Ptgs2,Hmox1,Icam1,Cd44,Mmp9,Ccl2,Socs3,Rhoc and Pdpn are important nodes in PPI network and may play an important role in Cerebral ischemia-reperfusion injury;(4)The fluorescence quantitative PCR results of rat cerebral ischemia-reperfusion model showed that the expressions of Stat3,Cxcl10,Atf3,Hmox1 and Mmp9 were increased,which played an important role in the injury caused by cerebral ischemia-reperfusion in rats.The results showed that cerebral ischemia-reperfusion injury was associated with increased gene expression of Stat3,Cxcl10,Atf3,Hmox1,Mmp9,TNF signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,cytokine cytokine receptor interaction and other signaling pathways.3.We constructed a rat cerebral ischemia-reperfusion model,which was divided into control group,ischemia-reperfusion group,and NMN treatment group after ischemia-reperfusion injury,and observed the therapeutic effect of NMN on Cerebral ischemia-reperfusion injury.In addition,oxygen deprivation experiments were conducted using PC-12 cell line in vitro to simulate the damage caused by hypoxia to cells,and the effect of NMN at the cellular level was observed.(1)NMN of500mg/kg can significantly inhibit the injury caused by Cerebral ischemia-reperfusion injury(P<0.05),alleviated the occurrence of apoptosis in brain tissue(P<0.01);(2)NMN significantly inhibited the proliferation of neutrophils induced by ischemia-reperfusion(P<0.05),could significantly inhibit the formation of extracellular trapping nets(P<0.01);(3)NMN can inhibit the ERK/P38 pathway;(4)NMN can salvage the inhibition of PC-12 cell proliferation caused by hypoxia at the cellular level(P<0.01),inhibited apoptosis induced by hypoxia(P<0.01),also inhibited the ERK/P38 pathway;(5)NMN can inhibit the production of ROS caused by cell hypoxia.The results showed that NMN could effectively reduce the injury caused by Cerebral ischemia-reperfusion injury and inhibit the occurrence of apoptosis,partly because it inhibited the formation of extracellular trapping net,and the mechanism was that it inhibited the ERK/P38 pathway. |
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