Effects Of Dexmedetomidine On Hypoxia-reoxygenation Injury In Rat Hippocampal Neurons And The Mechanism

Cerebral ischemia is a disease with insufficient blood flow in the brain.This can usually lead to a decrease in the metabolic rate and energy of the brain,and the consequent local cerebral infarction.When cerebral ischemia occurs,the supply of oxygen from the blood and the reduction in nutrients may cause hunger in the brain’s neuronal tissue.Hunger can induce cells to produce apoptosis,it has two diversion directions,one is to change in good direction:that is to restore survival,the second is to the bad direction of transformation: that is,into death.In terms of pathophysiology,reperfusion injury usually occurs when the blood supply returns to brain tissue after ischemia.Compared with ischemic injury,ischemia / reperfusion(I / R)may be caused by the destruction of the mitochondrial respiratory chain reaction and the excessive production of inflammatory mediators in the brain tissue area of ?the brain and the large amount of Ca2 + ions in the pulp Deposition in order to cause more damage to the neurons;in clinical surgery,including acute ischemic stroke and acute traumatic brain injury and many other brain diseases,can cause ischemia and reperfusion injury.Reperfusion injury is clinically considered an important determinant of secondary brain injuryMitochondria play an important role in regulating cell life activities.It moves at higher speeds in cells,through self-division or fusion with each other to achieve new individuals and can be formed in cells A close connection.Mitochondria are commonly referred to as "cell power plants",and their division and fusion are balanced,affecting functional and structural changes.Studies have shown that mitochondria by reducing cytochrome C,enzyme G and AFI factors such as the expression of apoptotic proteins in the regulation of programmed cell death plays an important role.In addition,studies have shown that mitochondrial calcium signaling pathway through the mitochondrial fission protein Drpl on acidification and dephosphorylation,affect the mitochondrial fission;so if the mitochondrial intake of calcium ions We can also reduce the mitochondrial splitting ability and reduce the number of splitting mitochondria.In our previous experiments,we have also found that the decrease of MCU activity and the inhibition of mitochondrial swelling and damage have a certain inhibitory effect on the infarct size and free oxygen production.This is a good expression of the transient I / R injury model in rats.Dexmedetomidine is a thrill to play its role in sedative and analgesic by selective,a major role in alpha 2 adrenergic receptor.Previous studies have demonstrated thatdexmedetomidine can prevent ischemia reperfusion of myocardium,kidney,intestine,liver and lung injury induced by brain injury.At the same time,Kuhmonen et al et al found that dexmedetomidine on middle cerebral artery occlusion in rats caused by cerebral infarction is of great benefit.dexmedetomidine can reduce inflammatory mediators induced Ca 2+ release and calcium overload reduce inflammation progress.The new study shows that dexmedetomidine can inhibit oxygen glucose deprivation or Ca2+induced mitochondrial swelling and maintaining mitochondrial morphology and function of stability,inhibited the hippocampal neuron calcium overload,reduced calcineurin activation,thereby inhibiting mitochondrial fission,its mechanism may be through inhibition of calcineurin activity,reduce the the phosphorylation of Drp1-ser637,thereby inhibiting the translocation of Drp1,combined with reduced mitochondrial outer membrane protein Fis1;in addition,it can inhibit the expression of Drp1-ser637 and Fis1,reducing their colocalization with the outer mitochondrial membrane,thereby inhibiting mitochondrial fission start.Therefore we assume that dexmedetomidine can inhibit calcium overload,by acting on the mitochondrial cytochrome c-cysteine protease pathway to reduce mitochondrial fission,thereby protecting neurons against I / R injury induced apoptosis,reduce apoptosis of neurons.Objective: To demonstrate the effect of dexmedetomidine(DEX)on the process of hippocampal neurons in hypoxia/reoxygenation(H/R)injury of mitochondria,and then explore the possible mechanism which might provide new targets for brain protection Methods:Sprague-Dawley rats were sacrificed in the hippocampus of the hippocampus.The neurons of the hippocampal neurons were collected and cultured on the 8th day..After 8d cultivation,the primary hippocampal neurons were randomly divided into six groups: control group(C group);vehicle group(V group);H/R group;H/R+DEX treatment groups: of D1,D2 and D3 group were added DEX 0.1,1,10 μmol/L during oxygen-glucose deprivation and reperfusion period.Culturing primary hippocampal cells were subjected to oxygen-glucose deprivation(OGD)for 6h,followed by 20 h of reperfusion.Cell apoptosis(by flow cytometry),fluorescence intensity of Ca2+(using a laser scanning confocal microscope),Ca N enzymatic activities(by ELISA),expression of Drp1,Fis1,Cyt C,caspase3(by western blot)were measured.Results Compared with C group and V group,cell apoptosis,fluorescence intensity of Ca2+,Ca N enzymatic activities were higher in H/R group(P<0.05)with the expression of Drp1,Fis1,Cytc,caspase3 increased.However 0.1,1,10 μmol/L could reduce the cell apoptosis,fluorescence intensity of Ca2+,Ca N enzymatic activities(P<0.05)with lower expression of Drp1,Fis1,Cytc,caspase3 compared with H/R group,in which 1 μmol/L could show the optimal treatment effect.Conclusion Dexmedetomidine 0.1,1,10μmol/Lcan significantly improve the rat hippocampal neurons in hypoxia-reoxygenation injury,of which 1 μ mol/L is the best protective concentration,the mechanism may be account with the right Inhibition of calcium overload-mediated mitochondrial fission and mitochondrial apoptotic pathways.