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Oxidative Stress Response And Expression Of Neurotransmitters In Intermittent Hypoxia

Posted on:2020-06-27Degree:MasterType:Thesis
Country:ChinaCandidate:L Q XuFull Text:PDF
GTID:2404330590998322Subject:Internal Medicine Respiratory diseases
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Sleep is important for maintaining the body's homeostasis and ensuring people's physical and mental health.In recent years,sleep-related diseases have received more and more social attention.Sleep apnea hypopnea syndrome is a type of sleep-disordered breathing disease,also a systemic disease.It is clinically common with obstructive,central and mixed diseases.Sex(both obstructive and central),with or without nighttime sleep hypopnea.Obstructive sleep apnea syndrome is a sleep-disordered disease caused by a variety of causes,resulting in nighttime hypopnea and daytime sleepiness.The clinically common cause is the narrowing of the upper respiratory tract.Long-term nighttime apnea and hypopnea,the body's hypoxia,blood system,nervous system,endocrine system and other systemic systems are affected by intermittent hypoxia,this hazard is extensive and irreversible,and even often sudden death at night.The treatment of this disease mainly includes surgery and non-surgery.Non-surgical treatment with nasal continuous positive airway pressure(NCPAP)is most effective.The purpose of surgical treatment is to eliminate or reduce airway obstruction,but this method is more individual.Strong,sometimes not completely cured,there will be recurrence of the disease.OSAS is inseparable from respiratory diseases,and the two syndromes are called overlapping syndrome clinically.Pulmonary heart disease is one of the most prominent diseases,and patients often have severe pulmonary hypertension and right heart failure.Due to respiratory dysfunction,long-term apnea at night makes the incidence of acute respiratory failure increase,resulting in severe breathing difficulties,cyanosis,convulsions and other manifestations.The treatment of obstructive sleep apnea is mainly ventilator therapy,which is used to dilate the airway,reduce the occurrence of nocturnal respiratory events,and prevent sudden death and complications caused by excessive ventilation.Oxidative stress plays an important role in the OSAS process.It can be linked to various signaling pathways such as TGF-b,NF-kb,and AMPK to promote the development of disease.In addition,the development of pulmonary fibrosis is also related to OSAS,possibly due to the activation of lung fibroblasts by intermittent hypoxia.In addition,in the previous clinical data statistics,we found that even if the severity of OSAS is different,and there are significant differences in family history,clinical symptoms,and nighttime indicators,a large proportion of these OSAS patients will be different.The extent of neurological symptoms,including daytime migraine,dizziness,and nighttime epilepsy,convulsions,and even many patients with depression.This intermittent hypoxic response of OSAS also has an effect on the expression of neurotransmitters in the cerebral cortex.Studies have shown that hypoxic damage can be achieved by recruiting inflammatory cells and factors,oxidative stress,leading to apoptosis of synaptic cells,impaired dopaminergic signaling,causing learning,memory and behavioral deficits,and cerebellar dysfunction.Oxidative stress is a manifestation of oxidation and anti-oxidation imbalance in the body.The active oxygen component produced by the body is toxic to tissue cells.If the antioxidant is reduced,the degree of oxidative stress in the body is increased,and the degree of resistance to external damage is reduced.The disorder of cell function leads to cell damage and apoptosis,and can even cause abnormal expression of protein translation.Although apoptosis is a common physiological mechanism,if oxidative stress is increased and endogenous or exogenous ROS are increased,it will be accompanied by an increase in apoptosis.Studies have shown that anti-oxidative stress,such as inhibition of NF-KB channel and SAPK channel can reduce apoptosis caused by oxidative stress,and the influence of oxidative stress on brain neurotransmitter expression and its mechanism are also worthy of discussion.Studies have shown that glial cells and neuronal cells in OSAS Injury and apoptotic reactions also occur.Neurological symptoms have caused us great interest.We used healthy adult male Sprague-Dawley rats in the Respiratory Laboratory of Tianjin Medical University General Hospital to perform OSAS rat modeling using intermittent hypoxic chambers.After the modeling,the content of 13 kinds of neurotransmitters including dopamine and adrenaline in the brain was determined by high performance liquid chromatography mass spectrometer.It was found that there was no statistical difference in GABA,and the neurotransmitters in other brains were different..Therefore,we hypothesize that the intermittent hypoxia mode of OSAS affects the secretion and uptake of neurotransmitters in the brain to a certain extent,which may cause corresponding neurological symptoms.In addition,we stained the lung slices after modeling,found that the lung structure was destroyed,the expression of mesenchymal cell markers was significantly increased,and there was epithelial-mesenchymal transition(EMT).The expression of oxidative index of lung fibroblasts under intermittent hypoxia simulation was significantly higher than that of the normal control group.In summary,we can draw corresponding conclusions:(1)OSAS common multiple neurological symptoms deserve attention.(2)OSAS has an oxidative stress effect and an EMT tendency.(3)OSAS affects the content of neurotransmitters in the cerebral cortex through hypoxic oxidative stress and inflammatory effects,including dopamine,homovanillic acid,serotonin,3,4-dihydroxyphenylacetic acid,norepinephrine,5-hydroxyindoleacetic acid,tryptophan,3-hydroxy kynurenine,3-hydroxy-2-aminophenylacetic acid,a decrease in the expression of adrenaline,an increase in the expression of kynurenine,may cause insomnia Factors related to neurological symptoms such as anxiety,depression,epilepsy,and memory loss.
Keywords/Search Tags:Sleep apnea, Neurotransmitters, Dopamine, Oxidative stress, Mass spectrometer
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