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The Effects And Mechanism Of Sevoflurane On Long-term Cognitive Function In Elder Rats With Vascular Cognitive Impairment

Posted on:2018-03-04Degree:MasterType:Thesis
Country:ChinaCandidate:L H JiangFull Text:PDF
GTID:2334330536486220Subject:Anesthesiology
Abstract/Summary:PDF Full Text Request
Due to the factors of the age,the elderly patients with the decline of important organ function and compensatory adjustment ability,very prone to postoperative cognitive dysfunction(POCD)under the stimulus such as operation.Besides,in the process of anesthesia,stress,hypoxygen and cyclic fluctuation and the use of related anesthetic drugs are likely to lead to elderly patients with the impairment of the basic brain function,such as information uptake,storage,reforming and process,which causing different degree of cognitive dysfunction.Vascular cognitive impairment(VCI)is vessel or vessel-related factors of cognitive dysfunction,is the early stages of cognitive function impairment and the formation and gradual degradation in the cognitive dysfunction,For the early detection or treatment the cognitive dysfunction,VCI has very important significance.Studies have showed that propofol,dexmedetomidine and parecoxib sodium,etc,the commonly used drugs in the clinical anesthesia could intervene in the inflammation and oxidative stress response of the central nervous system,improve the patient’s postoperative cognitive function,reduce the incidence of POCD.Different concentration of sevoflurane inhaled could exert brain protective effect by regulating cerebrovascular,cerebral blood flow,reducing intracranial pressure and cerebral metabolic rate of oxygen,but its impact on elderly patients POCD is controversial and its influence on VCI has yet to have a direct and systematic research.This study intends to explore the effects of sevoflurane on long-term impact of cognitive dysfunction in elder VCI rats and its mechanism,which aimed to provide basic research basis for the influence of POCD of sevoflurane on elderly patients.Objective To investigate the effects and mechanism of sevoflurane inhalation on the long-term cognitive function in elder VCI rats.Methods 120 female Wistar rats,aged 24~26 weeks and weighed 300 to 350 g,were randomly divided into 3 groups(n=40): Sham group(group A),VCI model group(group B)and VCI+sevoflurane inhalation group(group C).At the 4th and 8th weeks after model establishment,the shuttle box test and water maze test were used respectively to evaluate of cognitive function of three groups of rats.At the same time,the hippocampal tissue samples and blood samples were collected,the apoptosis index of hippocampal neurons was detected by TUNEL method,the apoptosis rate of hippocampal neurons and the calcium level in hippocampal neuron cytoplasm were detected by using flow cytometry technology,the mitochondrial membrane potential was determined by fluorescent probe technique;The activity of mitochondrial respiratory chain complexesⅠ~Ⅳ in rat hippocampal neurons homogenate,and the level of TNF-alpha,interleukin-1 beta in hippocampal tissue and blood samples were measured by ELISA.Results At the 4th and 8th week after modeling,the shuttle box test and water maze experiment shows the less electric shock numbers and more active of escape,and the learning and memory incubation cycle significantly shortened in sevoflurane inhalation treatment group rats compared with VCI rats model;Sevoflurane inhalation therapy could reduce the neuronal apoptosis rate and apoptosis index,reduce calcium concentration in the hippocampal neuronal cytoplasm,and improve the hippocampal neuron mitochondria membrane potential and the activity of the mitochondrial respiratory chain complexⅠ~Ⅳ in aged VCI rats at the 4th and 8th week after modeling;Moreover,Sevoflurane inhalation therapy could reduce TNF alpha and beta IL-1 in the hippocampus and blood samples and raised the of expression vascular endothelial growth factor(VEGF)in elder VCI rats at the same time.Conclusion Sevoflurane could effectively reduce the long-term cognitive dysfunction in elder VCI rats and its mechanism may be related to improve the level of VEGF expression,and promote the formation process of new blood vessels and reduce the inflammatory injury of rat hippocampal neurons induced by inflammation factor.
Keywords/Search Tags:Inflammation response, Sevoflurane, Cognitive function, Oxidative stress, Cerebral protection, Molecular mechanism
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