| [Background]:Postoperative cognitive dysfunction is a severe neurological complication that occurs after anesthesia and/or surgery for several days,months,or years of cognitive decline.The common clinical manifestations are memory,annotation,language comprehension,and information processing after anesthesia and/or surgery.Power and other cognitive dysfunction.The pathogenesis of POCD is not yet clear,and there are many influencing factors,among which age is the only independent risk factor known.POCD mainly occurred in the elderly patients,according to the results of the international POCD research cooperation group:the incidence of POCD at 7 and 3 months after the operation was 25.8%and 9.9%,respectively,for the elderly patients over 60 years of age.Anesthesia is a special unconscious state.It has some same neural regulatory mechanisms with the "sleep wake" rhythm.It is suggested that general anesthesia has different effects on the sleep awakening rhythm:propofol can move the sleep wake rhythm at the "sleep wake"junction,and the use of sevoflurane and isoflurane at the awakening period can offset the "sleep-Awakening" rhythm.The central controller of the circadian rhythm is located in the Suprachiasmatic Nucleus(SCN)of the hypothalamus,and the clock genes(such as Clock/Bmal1 and Per2/Cry1)play an important role in coordinating the physiological processes and behavioral activities of the body.Hippocampus is an important structure of learning and memory.Impairment of learning and memory function is considered to be an important manifestation of POCD.There is reliable evidence that circadian rhythm is an important basis for the formation of learning and memory.Animal tests showed that acetylcholine in the hippocampus showed a marked "sleep-Awakening" rhythm,increased acetylcholine release and decreased acetylcholine release under sleep.Further experiments showed that the change of sleep rhythm and the release of acetylcholine in hippocampus were significantly consistent under the action of isoflurane.Changes in circadian clock gene expression induced by isoflurane anesthesia need further exploration.Dexmedetomidine is an effective alpha 2-adrenergic receptor agonist,which is clinically applicable to the sedation of intubation and the use of ventilator patients during intensive care treatment.When dexmedetomidine is used for sedation,it has unique characteristics similar to natural sleep and easy to wake up.It can significantly improve sleep quality.The study shows that dexmedetomidine can improve the cognitive decline caused by isoflurane.This study intends to explore the effect of dexmedetomidin on the changes of SCN and hippocampal clock gene expression in the hypothalamic supramanasal nucleus induced by isoflurane anesthesia,and provide a new strategy for the diagnosis and treatment of POCD.[Method]:The animal type used in this experiment is SPF male C57BL/6 mice,2 month old,body weight 22-26g.Isoflurane anesthesia for continuous 6h inhalation anesthesia,dexmedetomidine diluted with normal saline,administered by intraperitoneal.The material was taken after the end of anesthesia.The process of the experiment is as follows:The mice were randomly divided into 4 groups:normal group of circadian rhythm(group C),anesthetic group(group A),right metoimidine preconditioning group(group Dex),dexmedetomidine preconditioning+anaesthesia group(group DexA).Dexmedetomidine preconditioning group(group Dex)and dexmedetomidine preconditioning+anaesthesia group(group DexA)were intraperitoneally injected with right metoimidin 50ug/kg half an hour before anesthesia,anesthesia group(group A)and right metomomidine preconditioning+anaesthesia group(group DexA)were treated with 6h isoflurane anesthesia.The natural time is converted to the circadian rhythm(CT),with the starting point of light at 8:00 for CTO.Anesthesia began in the relative awakening period of mice,that is,CT14 began,continued to CT20,anesthesia 6 h.SCN and hippocampal tissues were obtained when CT22,CT1,CT4,CT7,CT10,CT13,CT16 and CT19 were used.The expressions of Clock mRNA,Bmal1 mRNA and Per2 mRNA,Cry1 mRNA were measured by real-time quantitative polymerase chain reaction.[Results]:The expression of SCN and Clock mRNA,Bmal1 mRNA and Per2 mRNA,Cry1 mRNA expression of the hypothalamic suprachiasmatic nucleus in the hypothalamus of mice under anesthesia and normal circadian rhythm were rhythmical.The peak phase of Clock mRNA and Bmal1 mRNA in SCN and DexA groups in group C,group Dex and DexA group was near CT16.Compared with the C group,the peak phase of Clock mRNA and Bmal1 mRNA expression in SCN of group Dex mice did not shift,indicating that right metoimidin did not affect the circadian clock gene in the nucleus SCN of the hypothalamus hypothalamus under circadian rhythm.Compared with the C group,the peak phase shift of Clock mRNA and Bmal1 mRNA expressed in the SCN of group A mice lagged 6h,indicating that isoflurane anesthesia could lead to the change of the circadian rhythm of the SCN clock gene in mice Compared with the C group,the peak phase of Clock mRNA and Bmal1 mRNA expression in SCN of group Dex and DexA mice was not significantly offset,indicating that pre giving right metoomidin could regulate the peak phase shift of gene expression of SCN biological clock in mice induced by isoflurane anesthesia,and then improve the circadian rhythm.The peak phase of Per2 mRNA and Cry1 mRNA in SCN and DexA groups in group C,group Dex and DexA group was near CT1.Compared with the C group,the peak phase of Per2 mRNA and Cry1 mRNA expression in SCN of group Dex mice did not shift,indicating that right metoimidin did not affect the circadian clock gene in the nucleus SCN of the hypothalamus hypothalamus under circadian rhythm.Compared with the C group,the peak phase shift of Per2 mRNA and Cry1 mRNA expressed in the SCN of group A mice lagged 12h,indicating that isoflurane anesthesia could lead to the change of the circadian rhythm of the SCN clock gene in mice.Compared with the C group,the peak phase of Per2 mRNA and Cry1 mRNA in SCN and DexA mice did not significantly offset the peak phase of the expression of Per2 mRNA and Cry1 mRNA,indicating that the pre given dexmedetomidin could regulate the peak phase shift of the SCN biological clock gene expression in the mice induced by isoflurane anesthesia,and then improve the circadian rhythm.The peak phase of Clock mRNA and Bmall mRNA expression in the hippocampus of C group,Dex group and DexA group was near CT16.The peak phase of Clock mRNA in the hippocampus of group A mice and the peak phase of Bmall expressions were all near the CT16.Compared with the C group,the peak phase of the expression of Clock mRNA and Bmall mRNA in the hippocampus of Dex mice did not shift,indicating that right metomomidin had no effect on the circadian clock genes in the circadian rhythm.Compared with the C group,the peak phase shift of Clock mRNA and Bmall mRNA expression in the hippocampus of A mice was lagging behind 6h,indicating that isoflurane anesthesia could lead to the change of circadian rhythm of the hippocampus clock gene in mice.Compared with the C group,the peak phase of the expression of Clock mRNA and Bmall mRNA in the hippocampus of Dex and DexA mice did not significantly shift,indicating that the pre given dexmedetomidin could regulate the peak phase shift of the hippocampal clock gene expression in the hippocampus of the mice induced by isoflurane anesthesia,and then improve the circadian rhythm.The peak phase of Per2 mRNA and Cry1 mRNA expression in the hippocampus of C group,Dex group and DexA group was near CT1.The peak phase of Per2 mRNA in the hippocampus of group A mice and the peak phase of Cry1 expressions were all near the CT1.Compared with the C group,the peak phase of the expression of Per2 mRNA and Cry1 mRNA in the hippocampus of Dex mice did not shift,indicating that right metomomidin had no effect on the circadian clock genes in the circadian rhythm.Compared with the C group,the peak phase shift of Per2 mRNA and Cry1 mRNA expression in the hippocampus of A mice was delayed 12h.It indicated that isoflurane anesthesia could lead to the changes of the circadian rhythm of the hippocampus clock gene in mice compared with that of the C group.Dexmedetomidine can adjust the peak phase shift of hippocampal circadian clock gene expression induced by isoflurane anesthesia in order to improve circadian rhythm.[Conclusion]:Under normal circadian rhythm,SCN and hippocampal circadian clock genes are rhythmical,and isoflurane anesthesia can lead to a significant lag in the peak phase of its expression.Right metoimidin can regulate the phase lag of the SCN and hippocampal clock gene expression peaks caused by isoflurane anesthesia,and then improve the circadian rhythm. |
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