摘要
小型猪作为模式化动物在实验外科领域占据着重要位置，小型猪常被应用在人类解剖学、生理学、生物化学、药物筛选、疾病模型筛选、疾病发生机理、器官移植和胚胎移植等方面的研究。在进行与小型猪密切相关的课题时常常需要对其进行保定或进一步手术，所以小型猪的麻醉是进行相关研究工作的基础，小型猪麻醉成功、安全和药物选择、人员操作技术水平有直接关系，麻醉效果决定科研实验能否进顺利开展。目前，在猪临床麻醉中使用的麻醉剂种类繁多，给药途径有很多种，而且根据不同品系又开发出了特异性麻醉制剂。综合评价这些麻醉剂及其用药方式，可以发现它们有各自的优缺点。比如，肌肉注射麻醉剂需一次性注射足够剂量的麻醉剂，才能保证有稳定的麻醉时间和麻醉效果，但是其麻醉诱导时间和维持时间较长，麻醉深度无可控性；静脉麻醉具有作用迅速，麻醉深度可控等优点，但往往需要麻醉诱导，并且维持过程需要调整多种药物的注射，操作较繁琐；吸入麻醉相对可以提供可控的麻醉时间和麻醉效果，但其需特殊吸入麻醉设备并且要求技术人员具有熟练的操作技术。基于目前麻醉现状，本课题组进行小型猪新型麻醉方法的探索，将液态异氟醚融入脂肪乳通过静脉注射方式进行小型猪全身麻醉，前期研究发现此麻醉剂具有以下优点：一、经静脉给药将麻醉药直接经血液循环进行血脑屏障到达麻醉作用部位而快速产生麻醉作用；二、可通过调节静脉输注速度来调节麻醉深度，停药后苏醒迅速；三、从血中排出到肺泡中的挥发性麻醉药可以经肺泡重新吸收入血，以减少静脉麻醉药用量，用药量是吸入麻醉用量的1/3-1/4；四、不需要挥发罐，减少临床繁琐操作步骤，可使麻醉费用降低；五、乳化制剂对动物心肌具有保护作用。
为了探究乳化异氟醚在小型猪全身麻醉上应用的可行性，进行了全身麻醉最佳静脉注射速度筛选、麻醉效果和安全性评价试验，麻醉过程中监测的指标有，常规指标、生物反射、麻醉效果、呼吸系统、循环系统、心电图和脑电图。为了进一步阐述其全身麻醉分子机理，进行了相关实验。首先，对麻醉前后各脑区信号转导通路中突触体Na+-K+-ATP酶、Ca2+、Mg2+-ATP酶以及NO-NOS-cGMP信号通路各组分的活性和含量变化进行测定；其次，通过免疫组织化学方法把麻醉前后各脑区NMDAR和nAChR阳性细胞分布和表达情况进行测定；再次，通过蛋白质印迹法检测c-fos和c-jun基因蛋白在不同脑区的表达情况。
试验结果如下：
1．小型猪乳化异氟醚麻醉最小输注率筛选试验
小型猪以临床剂量丙泊酚进行麻醉诱导，乳化异氟醚静脉注入维持麻醉，通过序贯法和自身交叉法确定最佳注射速度为2.8mL/kg.h。
2．小型猪乳化异氟醚麻醉监测实验
小型猪以最小输注率进行麻醉，在麻醉过程进行一般生理指标、呼吸和循环系统指标、心电和脑电图监测，结果表明，乳化异氟醚具有理想的麻醉效果，并且对生理指标、呼吸和循环指标影响轻微，心功能无异常，脑电图波型提示小型猪处于适宜的麻醉深度。
3．乳化异氟醚全麻的中枢细胞信号转导机制的研究
（1）麻醉期大鼠大脑皮质、海马、丘脑突触体Na+-K+-ATP酶活性降低，恢复期酶活性趋近麻醉前，酶活性变化与麻醉深度变化呈一致性，表明：大脑皮质、海马、丘脑突触体Na+-K+-ATP酶可能参与了乳化异氟醚产生全麻作用的调控过程。
（2）麻醉期大脑皮质、小脑、海马和丘脑突触体Ca2+-ATP酶活性受到抑制，恢复时活性增强，其酶活性变化趋势与麻醉深度变化一致。表明：表明大脑皮质、小脑、海马、丘脑中突触体Ca2+-ATP酶可能参与了乳化异氟醚产生全麻作用的调控过程。
（3）麻醉期大脑皮质和海马突触体Mg2+-ATP酶活性受到抑制，恢复期呈上升趋势，其变化趋势与麻醉深度变化一致。表明：大脑皮质和海马中Mg2+-ATP酶可能参与了乳化异氟醚产生全麻作用的调控过程。
（4）麻醉前后大脑皮质和海马中NO含量、NOS活性和cGMP含量变化趋势一致，并且与大鼠麻醉深度变化具有同步性。表明：大脑皮质和海马中NO-NOS-cGMP信号通路可能参与了乳化异氟醚产生全麻作用的调控过程。
4．乳化异氟醚麻醉对NMDAR2B和nAChRα4表达的影响
麻醉期，大脑皮质层NMDAR2B的阳性细胞增加，恢复期阳性细胞减少至对照组水平；海马NMDAR2B在麻醉期阳性细胞减少，恢复期增加至对照组水平。表明，乳化异氟醚可能是通过诱导大脑皮质NMDAR2B表达和抑制其在海马中表达来调控麻醉过程。NMDAR2B可能是乳化异氟醚全身麻醉作用的靶位之一。
在由麻醉期到恢复期过程中，nAChRα4在大脑皮质层和海马中阳性细胞由减少到恢复至对照组水平，在小脑和脑干中nAChrs阳性细胞由增加到减少。表明，乳化异氟醚可能是通过诱导nAChrs在大脑皮质、海马中表达和抑制在小脑和脑干中表达来调控麻醉过程，nAChRα4可能是乳化异氟醚全身麻醉作用的靶位点。
5．乳化异氟醚麻醉对c-fos和c-jun基因蛋白表达的影响
麻醉期，大脑皮质、丘脑、海马和脑干c-fos蛋白表达均增加，恢复组各区c-fos基因蛋白表达减少至对照组水平，c-fos蛋白表达量变化与麻醉深度变化一致，表明大脑皮质、丘脑、海马和脑干中c-fos基因参与了麻醉调控过程，是乳化异氟醚全身麻醉作用的靶基因之一。
麻醉期，小脑、海马和脑干中c-jun蛋白表达显著增加，在恢复期表达降低至麻醉前水平，c-jun蛋白表达量变化与麻醉深度基本一致，表明小脑、海马和脑干中c-jun基因参与了麻醉调控过程，是乳化异氟醚全身麻醉作用的靶基因之一。
综合以上，本实验证明了乳化异氟醚在小型猪全身麻醉中应用的可行性、可靠性和安全性，乳化异氟醚静脉用药可以作为小型猪一种新型麻醉方法在临床中推广应用；实验从组织、细胞和基因多层次、较系统地对乳化异氟醚的麻醉机理进行阐述，为其科学合理的在小型猪全身麻醉中应用奠定理论基础。
Miniature pigs as modeled animals, occupy the important position in the field of experimentalsurgery. Today, they are often used in human anatomy, physiology, biochemistry, drug screening,disease model screening, disease mechanism, organ transplantation and embryo transplantationresearch. Experiment about the miniature pig often need to carry on the immobilization or furthersurgery, so miniature pigs anesthesia should pay much attention as a research direction. Safety,drug selection and personnel technical level have directly relationship with the success ofminiature pigs anesthesia. Further research can be proceeded or not depending whether anesthesiasucceed or not. At present, various types of anesthetic used in clinical anesthesia pigs.Anesthetic has been applied for many kinds of ways. Specific anesthetic agents have been used fordifferent pig's strains. Comprehensive evaluation of these anesthetics and method ofadministration, it can be found that they have their own advantages and disadvantages.Intramuscular injection, for example, a one-time injection anesthetic doses of anesthetic, enough toguarantee a stable anesthesia time and anesthesia effect, but its anesthetic induction time andmaintain for a long time, no anesthesia depth controllability; Intravenous anesthesia haveadvantages of shorter onset time and anesthesia depth control, but often require anesthesiainduction, and maintain the process need to adjust a variety of anesthetics, operation wascomplicated; Relative inhalation anesthesia can provide controlled time and anesthesia effect, butit need special inhalation anesthesia equipment and technical personnel with skilled operationtechniques. Based on the present situation of anesthesia, the research on new miniature pigsanesthetic method of exploration, the liquid isoflurane to miniature pigs into the intravenous fatemulsion by general anesthesia. Previous studies have found that this anesthetic method has thefollowing advantages: One, the anesthetics has direct effects on anesthetic effect parts to produceanesthetic effect rapidly, anesthetics can across the blood brain barrier in blood circulation byvein injection; Two, By adjusting the intravenous infusion speed to control the depth of anesthesia,after withdrawal to quickly; Three, blood from the vent to alveolar of volatile anesthetics can thealveolar reabsorbed into the blood, to reduce the intravenous drug dosage, there is inhalationanesthesia dosage of1/3to1/4; Four, do not need to volatile tank, reduce clinical trival operationsteps, can make the anesthesia cost reduced; Five, emulsifying agents for animals with myocardialprotection.
To explore emulsified isoflurane has the feasibility of the application in miniature pig generalanesthesia. The selection of best speed of intravenous general anesthesia, anesthesia effect and thesafety evaluation test were been done. Anesthesia monitoring indicators includes conventionalindicators, biological reflex, the effects of anesthesia, respiratory system, circulatory system, ECGand EEG in the process of anesthesia. The related experiment were been done to investigate themolecular mechanism of general anesthesia. First of all, changes of synaptosome activity andcontent about Na+-K+-ATPase, Ca2+,Mg2+-ATPase and each composition of NO-NOS-cGMP signalpathways before and after the anaesthesia in brain signal transduction pathways; Second,distribution and expression of of NMDAR and nAChR positive cells before and after theanaesthesia in various brain regions by immunohistochemical method; Third, the c-fos and c-jungene protein expression were detected in different brain regions by protein imprinting method.
Experimental results such as follows:
1. Miniature pig emulsified isoflurane anesthesia minimum injection rate screening test
Miniature pigs to3.5mg/kg dose of propofol by ear marginal vein push note30-45sanesthesia induction, intravenous injection of7%emulsified isoflurane to maintain anesthesia, bysequential method and determine the optimal injection itself the crossover rate was2.8ml/kg. h.
2. Small pig emulsified isoflurane anesthesia monitoring experiment
Miniature pigs had been anesthetized with minimum injection rate, monitoring generalphysiological indexes, breathing, circulation index, ECG and EEG during the procedure.Emulsified isoflurane can guarantee good anesthetic effect, and little effects on physiologicalindexes, breathing, circulation indexes, no abnormal heart function, EEG waveform shows thatsmall pig in good depth of anesthesia.
3. Emulsified isoflurane central cell signal transduction mechanism research
（1） In the rat cerebral cortex, hippocampus, thalamus synaptosome Na+-K+-ATPase activityis restrained, the recovery of enzyme activity approach before anesthesia, enzyme activity isclosely related to anesthesia depth changes, the results showed that the cerebral cortex,hippocampus, thalamus synaptosome Na+-K+-ATPase may participate in the regulation process ofemulsified isoflurane anesthesia action.
（2） Anesthesia phase of the cerebral cortex, cerebellum, hippocampus, and thalamussynaptosome Ca2+-ATP enzyme activity is restrained, enhanced recovery activity, its enzymeactivity change trends and anesthesia depth changes are closely related. The experimental resultsshow that in the cerebral cortex, cerebellum, hippocampus, thalamus synaptosome Ca2+-ATPasemay participate in the regulation process of emulsified isoflurane anesthesia action.
（3） Anesthesia phase of the cerebral cortex and hippocampal synaptosome Mg2+-ATPaseactivity is restrained,recovery is on the rise,its change trend with the depth of anesthesia. Theresults showed that the cerebral cortex and hippocampus Mg2+-ATPase may participate in theregulation process of emulsified isoflurane anesthesia.
（4） Anesthesia in cerebral cortex and hippocampus in the process of the NO content andNOS activity and cGMP content change trend is consistent,and consistent with changes in thedepth of anesthesia in rats, the results show that the NO-NOS-cGMP signal pathway in cerebralcortex and hippocampus may be involved in the regulation process of emulsified isofluraneanesthesia.
4. NMDAR2B and nAChRα4receptor expression effect of emulsified isoflurane to rat differentbrain regions
Anesthesia period NMDAR2B expression of cortex in the brain increases with depth ofanesthesia deepens, recovery expression decrease with depth becomes shallow; Granular cell layerof hippocampus during the process of anesthesia NMDAR2B expression decrease with depth ofanesthesia deepens, recovery increase. Experimental results show that the emulsified isofluranecould be induced by cerebral cortex increased NMDAR2B expression and expression inhippocampus decreased to control anesthesia process.
By the anaesthesia period to the recovery process nAChRα4in the brain cortex andhippocampus from expression decrease to increase, in the cerebellum and brainstem nAChRα4reduced from expression to expression. The results showed that the emulsified isoflurane could beinduced by increased nAChRα4expression in cerebral cortex and hippocampus, inducedexpression to reduce regulation in the cerebellum and brain stem anesthesia process.
5. The protein expression influence of emulsified isoflurane to c-fos, c-jun gene in rat differentbrain regions.
After injection of emulsified isoflurane, except cerebellum,all brain regions c-fos proteinexpression increased. c-fos gene protein expression was decreased inrecovery group, the resultsshow that cfos gene in the brain cortex, hypothalamus, hippocampus and brain stem may beinvolved in the regulation process of emulsified isoflurane anesthesia.
Emulsified isoflurane anesthesia in the cerebellum, hippocampus and brain stem c-jun proteinexpression was significantly increased, expressed in recovery period reduced to levels of beforeanesthesia, the results show that the c-jun gene in the cerebellum, hippocampus and brain stemmay be involved in the regulation process of emulsified isoflurane anesthesia.
Comprehensive above, the experiment proved that the emulsified isoflurane have advantagesof feasibility, reliability and security in miniature pigs general anesthesia. Intravenous injection ofemulsified isoflurane can be used as a new type anesthesia methods in miniature pig’s clinicalapplication; Experiment from tissue, cell and gene levels, was systematically elaborated theanesthesia mechanism of emulsified isoflurane. These provide scientific and reasonabletheoretical basis for application of emulsified isoflurane in miniature pigs general anesthesia.
引文
[1]林德贵．2004．兽医外科手术学（第四版）[M]．中国农业出版社，42-44．
[2]范宏刚，刘焕奇，王洪斌等．麻醉性镇痛药研究进展[J]．动物医学进展，2008，29（1）：77-80.
[3]王书林．兽医临床诊断学[M].中国农业出版社，2003：397．
[4]庄心良，曾因明，陈伯銮．现代麻醉学[M].人民卫生出版社，2003：1893-2001．
[5]范明普，杨焕民，刘皙洁，等.846合剂和戊巴比妥钠联合对香猪进行全身麻醉的效果观察[J].黑龙江畜牧兽医，1994，（5）：22-23．
[6]常国友，马诺山，付小兵，等．实验用小型猪麻醉效果观察[J].上海实验动物科学，1995，15（3）：171-172．
[7]粟瑞福，乔伯英，訾文敏．氯胺酮和戊巴比妥钠对于小型猪麻醉效果的观察[J]．实验动物科学与管理，1995，12（1）：28-30．
[8]周忠信，王捷，赵善广．戊巴比妥钠腹腔麻醉在小型猪中的应用[J]．上海实验动物科学，2001，21（2）：113．
[9]孙同柱，付小兵，方利君，等．两种麻醉方法对小型猪麻醉效果的比较[J].上海实验动物科学，2003，23（4）：238-239．
[10]吴曙光，余小明，田锟，等．速眠新Ⅱ对幼龄贵州小型猪外科手术中的应用研究[J].实验动物科学与管理，2006，123（4）：21．
[11]钟海燕，孟兴凯，丁翠霞．小型猪麻醉的实验室观察[J].内蒙古医学院学报，2006，28（2）：119．
[12]张栋，郁佩华，刘天云．一种麻醉方法对实验小型猪的效果观察[J].实验动物科学，2008，25（4）：64-65．
[13]范宏刚，胡魁，卢德章，等．复合麻醉剂（XFM）对小型猪效果观察[J]．中国兽医杂志，2009，45（11）：63-64．
[14]王建发．常用动物复合麻醉药物[J]．北方牧业，2008，13（7）：26．
[15]王喆，陆承荣，罗渊，等．氯胺酮与硫喷妥钠复合麻醉对五指山小型猪麻醉效果的观察[J].中国畜牧兽医，2011，38（05）：227-228．
[16]颜克松，牛春，王英召，等．氯胺酮与速眠新复合应用对小型猪麻醉的观察[J].中国畜牧兽医，2010，37（5）：206-207．
[17]宋兵，祁亮，任旭东，等．小型猪心内直视手术两种麻醉方法的对比研究[J].西安交通大学学报，2010，31（3）：363-364．
[18] Kaiser GM， Fruhauf NR， Zhang HW，et al． Intravenous infusion anesthesia withpropofol-midazolam-fentanyl for experimental surgery in swine[J]. J Invest Surg，2003，16（6）：353-356．
[19] Goldmann C， Ghofrani A， Hafemann B， et al． Combination anesthesia withKetamine and Pentobarbital： a longterm porcine model[J]. Res Exp Med，1999，199：35．
[20] Fruhauf NR，Oldhafer KJ，Holtje M，etal．Bioartificial liver support system using primaryhepatocyte preclinical study in a new porcine hepatectomy model[J]. Surgery，2004，136（1）：47-52．
[21]李纪平，李明，王朝军，等．吸入麻醉在小型猪无菌剖腹产中的使用效果观察[J]．中国兽医杂志，2005，41（5）：21-22．
[22]丁德忠，李显达，屠玮等．实验用小型猪吸入性全麻效果观察[J].黑龙江畜牧兽医，2007，（11）：64-65．
[23]王洋，王承利，张贺．异氟醚吸入麻醉在巴马小型猪中的应用[J]．中国比较医学杂志，2010，20（10）：38-39．
[24]王凯，黄丽洁，苟鹏，等．小型猪的麻醉及气管插管技术[J].实验动物科学.2011.28（1）：50-51．
[25] Piermattei DL，Swan H． Techniques for general anesthesia in miniature pigs[J]. J. Surg.Res.1970，26（10）：587．
[26] John F Boylan，Davy CH Cheng， Alan N Sandler，et al．Cocaine toxicity and isofluraneanesthesia: Hemodynamic， myocardial metabolic， and regional blood flow effects inswine[J]. Journal of Cardiothoracic and Vascular Anesthesia，1996，10（6）：773-774．
[27] Kazutoshi K，Itaru N，Hidehiro N，et al． A Subacute hypoxic model using a pig[J]. SurgeryToday，2005，35（11）：951-954．
[28] Schulz R， Walz MK， Behrends M， et al． Minimal protection of the liver by ischemicpreconditioning in pigs[J]. Am J Physiol Heart Circ Physiol，2001，280：198．
[29] Finch JG， Fosh BG，Anthony AA，et al． The use of a liquid electrode in hepaticelectrolysis[J]． J Surg Res，2004，120：272．
[30] Haga HA， Ranheim B，Spadavecchia C． Effects of isoflurane upon minimum alveolarconcentration and cerebral cortex depression in pigs and goats: an interspeciescomparison[J]． Vet J，2011，187（2）：217-220．
[31] C Spadavecchia，HA Haga， B Ranheim． Concentration-dependent isoflurane effects onwithdrawal reflexes in pigs and the role of the stimulation paradigm[J]． The VeterinaryJournal，2012，194（3）：375-379．
[31]梁小民.乳化异氟醚实验室研究[D].重庆医科大学博士论文，2003，266-267.
[32] Salman KN，Rozman RS，Cascorbi HF，et al. Intravenous administration ofa new volatileanesthetie，2，2-dichlor-l，l-difluoroethyl methylsulfide，in dogs and monkeys[J]. Am J VetRes，1968，29（l）：165-72.
[33] Caseorbi HF，Helrieh M，Krantz JC Jr，et al. Hazards of mcthoxyfiurane emulsions inman[J].AnesthAnalg，1968，47（5）：557-559.
[34] Biber B， Martner J， Werner O. Halothane by the I.V rout in experimentalanimals[J].Aetaanaesth，1982，26：658-659.
[35] Eger RP，Macleod BA. Anaesthesia by intravenous emulsified isfolurane in mice[J].Canadian joumal of anaesthesia，1995，42（2）：173-176.
[36] Jeffrey B，Musser DO，John L，et al.The anesthetic and Physiologic effects of an intravenousadministration of a halothane lipid emulsion（5%vol/vol）. Anesth Analg，1999，88：671-675.
[37]徐茜，陈玉培.静脉乳化异氟醚的研究进展[J].医学综述，2008，14（15）：2350-2353.
[38]刘陕岭，刘进.乳化异氟醚和脂肪乳对大鼠心脏缺血再灌注损伤的影响[J].华西药学杂志，2007，22（5）：525-527.
[39]林海霞，罗南富，刘进，等.乳化异氟醚灌胃对大鼠的镇静催眠作用与安全性[J].四川大学学报，2010，41（5）：862-864.
[40]马汉祥，李杰，杨宗斌，等.犬静脉注射乳化异氟醚与异丙酚麻醉的效果[J].中华麻醉学杂志，2006，26（9）：862-863.
[41]柴云飞.乳化异氟醚局部麻醉作用研究[D].四川大学临床医学博士专业学位论文，2007，89-93.
[42]杨静，龚春雨，柴云飞，等.选择性外周神经给乳化异氟醚山羊模型的建立[J].四川大学学报，2010，41（2）：332-336.
[43]段志祥，杨保仲.腹腔注射异氟醚、乳化异氟醚对小鼠肌肉松弛作用的观察[J].中国医疗前沿，2012，7（3）：41-42.
[44]孙海峰，王泉云，梁小民，等.乳化异氟醚腹腔注射对大鼠的麻醉作用与安全性[J].中华麻醉学杂志，2004，24（1）：51-53.
[45]谭兴琴，陈玉培，张文胜，等.乳化异氟醚对缺氧复氧乳鼠心肌细胞的保护作用及bcl-2、bax表达的影响[J].第三军医大学学报，2008，30（17）：1611-1614.
[46]张雷，顾尔伟，刘训芹，等.乳化异氟醚后处理对兔在体心脏缺血/再灌注损伤的保护作用[J].中国药理学通报，2009，25（10）：1322-1325.
[47]邱燕，黄瀚，刘进，等.乳化异氟醚心脏停跳液对犬心肌损伤的保护作用[J].四川大学学报，2010，41（4）：703-705.
[48]冯昌栋，戴体俊.异氟醚全麻机制的研究进展[J].《国外医学》麻醉学与复苏分册，2002，23（6）：327-329.
[49] Kindler CH. Mechanisms of action of inhalation anesthesia: from Meyer-Overton into thenew millennium[J]. Schweiz Rundsch Med Prax，2002，91（21）：920-924.
[50] Ueda I. Molecular mechanisms of anesthesia[J]. Keio J Med，2001，50（1）：20-25.
[51] TB Dzikitia， GF Stegmanna， LN Dzikiti，et al. Effects of midazolam on isofluraneminimum alveolar concentration in goats[J]. Small Ruminant Research，2011，97：104–109.
[52] Bozkus H， Crawford NR， Chamberlain R H，et al. Comparative anatomy of the porcine andhuman thoracic spines with reference to thoracoscopic surgical techniques[J].SurgicalEndoscopy，2005，19（12）：1652-1665.
[53] Brazaluk AZ， Mozgovaia EN， Suchilina SP， et al. Effect of combined anesthetics on theactivity of various myocardium enzymes[J]. Ukr Biokhim Zh，1987，59（3）：79-82.
[54] Jerry M， Gonzales MD， Iris BS. Pentobarbital enhances Cyclic adenosine monophosphateproduction in the brain by effect on neurons but no glia[J]. Anesthesiology，1996，84：1148-1155.
[56] Satoh E，Nakazato Y. On the mechanism of ouabain-induced release of acetylcholine fromsynaptosomes[J]. J Neurochem，1992，58（3）：1038-1044.
[57] Andrzejowski J，Sleigh JW， Johnson IA，et al. The effect of intravenous epinephrine on thebispectral index and sedation[J].Anaesthesia，2000，55(8)：761-763.
[58] Barzago MM，Bortolotti A，Stellari FF，et al. Respiratory and hemodynamic functions，blood-gas parameters，and acid-base balance of ketamine-xylazine anesthetized guinea pigs[J].Lab Anim Sci，1994，44（6）：648-650.
[59] Tobin JR， Martin LD，Breslow MJ，et al. Selective anesthetic inhibition of brainnitric oxidesynthase[J]. Anesthesiology，1994，81：1264-1269.
[60] Glauser DA，Sch legel W. Mechanisms of transcriptional regulation underlying temporalintegration of signals [J]. Nucleic Acids Res，2006，34（18）：5175-5183.
[61] Akhouayri O，Starnaud R. Differential Mechanisms of Transcriptional Regulation of theMouse Osteocalcin Gene by Jun Family Members[J]. Calcified Tissue International，2007，80（2）：123-131.
[62] Silva AJ. Molecular and cellular cognitive studies of the role of synaptic plasticity inmemory[J]. J Neurobiol，2003，54(1)：224.
[63] Monje P， Marinissen MJ， Gutkind JS. Phosphorylation of the carboxyl-terdminaltransactivation domain of c-fos by extracellular signal-regulated kinase mediates thetranscriptional activation of AP-1and cellular transformation reduced by plateletderivedgrowth factor[J]. Mol Cell Biol，2003，23(19)：7030-7043.
[64] Nestler EJ. Historical renew: Molecular and celluhar mechanisms of opiate and cocaineaddiction[J].Trends Pharmacol Sci，2004，25（4）：210.
[65] Murali G，Subbarao B. Immunoglobulin Gene Rearrangements， Oncogenic Translocations，B-Cell Receptor Signaling， and B Lymphomagenesis[J]. Cancer Genetics，2010，5：399-425.
[66] Satoh E，Nakazato Y. On the mechanism of ouabain-induced release of acetylcholine fromsynaptosomes[J].J Neurochem，1992，58（3）：1038-1044.
[67] Olsen AK，Bladbjerg EM，arckmann P，et al. The G ttingen minipig as a model forpostprandial hyperlipidaemia in man:experimental observations[J]. Lab Anim，2002，36（4）：438-444.
[68] Moncada S，Higgs EA. The L-Arginine nitric oxide pathway [J]. N Eng J Med，1993，329：2002-2012.
[69] Lin HC，Baird AN，Pugh DG，et al. Effects of carbon dioxide insufflation combined withchanges in body position on blood gas and acid-base status in anesthetized llamas[J].VetSurg，1997，26(5)：444-450.
[70] Krnlevic K， Puil E. Halothane suppresses slow inward currents in hippocampalslices[J].Can J Physiol Pharmacol，1988，66：1570-1575.
[71] Richards CD. What the actions of anaesthetics on fast synaptic transmission reveal about themolecular mechanism of anaestrhesia[J].Toxicolotry Letteis，1998，100(101)：41-50.
[72] Pocock G，Richards CD. Excitatory and inhibitory synaptic mechanisms in anaesthesia[J]. BrJ Anaesth，1993，71：134-147.
[73] Mao L，Wang JQ. Group I metabotropic glutamate receptormediated calcium signaling andimmediate early gene expression in cultured rat striatal neurons[J]. Eur J Neurosci，2003，17：741-750.
[74] Eaton ME，Macias W，Youngs RM，et al. L-type Ca2+channel blockers promoteCa2+accumulation when dopamine receptors are activated in striatal neurons[J]. Mol BrainRes，2004，131：65-72.
[75] Wang JQ，Fibuch EE，Mao L. Regulation of mitogen-activated protein kinases by glutamatereceptors[J]. J Neurochem，2007，100(1)：1.
[76]李雪吟，冯琳，刘扬，等.第二信使环腺苷二磷酸核糖介导Ca2+释放的作用机制[J].动物营养学报，2011，23（12）：2043-2047.
[77] David A，Jacobson LH，Philipson. Ion Channels and Insulin Secretion[J]. Pancreatic BetaCell in Health and Disease，2008，2：91-110.
[78] West AE， Chen WG， Dalva MB， et al. Calcium regulation of neuronal gene expression[J].Proc Natl Acad Sci，2001，98：11024-11031.
[79]陈翔，杨于嘉. NMDA受体与脑报伤[J].国外医学生理、病理科学与临床分册，1996，16：178-180.
[80] Yamg J， Woodhall GL，Jones RS. Tnic facilitation of glutamate release by presynapticNR2B-containing NMDA receptors is incresed in the entorhinal cortex of chronicallyepileptic rats[J]. J Nemrosci，2006，26(2)：406-410.
[81] Dhiraj K， Raina D，Ravichandran S，et al. Cellular phosphatases facilitate combinatorialprocessing of receptor-activated signals[J]. BMC Research Note，2008，1(1)：81.
[82]徐文洪.离子通道的调控和受体依赖的离子通道研究进展[J].中国药理学通报，1997，13（5）：401-404.
[83]谭红鹰，菊地龙明，曾维安，等.异氟醚麻醉对大鼠海马乙酰胆碱释放昼夜节律的影响[J].中山大学学报医学科学版，2008，29（6）：758-762.
[84]薛庆生，于布为.神经元烟碱受体在全身麻醉机制中的作用[J].生理科学进展，2003，34（1）：37-41.
[85]吴安石，岳云，龙健晶，等.不同浓度异氟醚对大鼠海马乙酞胆碱释放的影响[J].中华麻醉学杂志，2005，25（1）：58-59.
[86]张勤功，赵丽，赵嘉训，等.普鲁卡因静脉麻醉对中枢性乙酰胆碱释放影响的研究[J].肿瘤研究与临床，2005，17（4）：244-246.
[87] Nakayama T，Hashimoto T，Nagai Y. Involvement of glutamate and gamma-aminobutyricacid （GABA）-ergic systems in thyrotropin-releasing hormone-induced rat cerebellar cGMPformation[J]. Eur J Pharmacol，1996，316（2-3）：157-164.
[88] Wexler EM，Stanton PK，Nawy S. Nitric oxide depresses GABAA receptor function viacoactivation of cGMP-dependent kinase and phosphodiesterase[J]. J Neurosci，1998，18（7）：2342-2349.
[89] Wang Xiaojing，Li Zhengli，Zhu Changgeng，et al. Effects of activated ACM on expressionof signal transducers in cerebral cortical neurons of rats[J]. Journal of Huazhong Universityof Science and Technology，2007，27（3）：230-232.
[90] Shin WJ，Winegar BD. Modulation of noninactivating K+channels in rat cerebellar granuleneurons by halothane，isoflurane，and sevoflurane[J]. Anesth Analg，2003，96（5）：1340-1344.
[91] Singh G，Janicki PK，Horn JL，et al. Inhibition of plasma membrane Ca （2+）-ATPase pumpactivity in cultured C6glioma cells by halothane and xenon[J]. Life Sci.1995.56（10）：219-224.
[92] Ouyang W，Wang G，Hemmings HC. Isoflurane and propofol inhibit voltage-gated sodiumchannels in isolated rat neurohypophysial nerve terminals [J]. Mol Pharmacol，2003，64（2）：373-381.
[93] Gang W，Kiyoshi K， Gregory G. Divergent signaling pathways mediate induction of Na，K-ATPase α1and β1subunit gene transcription by low potassium[J]. Curr Drug Target CNSNeurol Disord，2007，294：73-85.
[94] Haroon A，Sungho H， Erik D. Controlling Ca2+-Activated K+Channels with Models of Ca2+Buffering in Purkinje Cells[J]. The Cerebellum，2010，27：234-241.
[95] Ouyang W，Wang G， Hemmings HC. Isoflurane and propofol inhibit voltage-gated sodiumchannels in isolated rat neurohypophysial nerve terminals[J]. Mol Pharmacol，2003，64（2）：373-381.
[96] Lingamaneni R， Birch ML， Hemmings HC Jr. Widespread inhibition of sodium channe-ldependent glutamate release from isolated nerve terminals by isoflurane and propofol.Anesthesiology，2001，95：1460-1466.
[97] Jiang Y， Ruta V， Chen J， et al. The Principle of Gating Charge Movement in a VoltageDependent K+Channel [J]. Nature，2003，423(6935)：42-48.
[98] Shin WJ，Winegar BD. Modulation of noninactivating K+channels in rat cerebellar granuleneurons by halothane, isoflurane, and sevoflurane[J]. Anesth Analg，2003，96（5）：1340-1344.
[99] Fomitcheva I， Kosk KD. Volatile anesthetics selectively inhibit the Ca（2+）-transportingATPase in neuronal and erythrocyte plasma membrane[J]. Anesthesiology，1996，84（5）：1189-1195.
[100] Randall A， Benham CD. Recent advances in the molecular understanding of voltage-gatedCa2+channels. Mol Cell Neurosci，1999，14：255-272.
[101] Takei T, Saegusa H, Zong S, et al. Anesthetic sensitivities to propofol and halothane in micelacking the R-type Ca2+channel [J]. Anesth Analg，2003，97（3）：683.
[102] Ramazan B，Donata O. Voltage-activated Calcium Currents in Octopus Cells of the MouseCochlear Nucleus[J]. Journal of the Association for Research in Otolaryngology，2007，8(4)：509-521.
[103] Parekh AB，Putney JW. Store operated calcium channel[J]. Physiol Rev，2005，85（2）：757-810.
[104] Belelli D，Lambert JJ，Peters JA，et al. The interaction of the general anesthetic etomidatewith the gamma-aminobutyric acid type A receptor is influenced by a single amino acid[J].Proc Natl Acad Sci USA，1997，94（20）：11031-11036.
[105] Franks JJ， Horn JL，Janicki PK， et al. Stable Inhibition of Brain Synaptic PlasmaMembrane Calcium ATPase in Rats Anesthetized with Halothane[J]. Anesthesiology，1995，82：118-128.
[106]孙众芜，陈军．全麻药的分子和细胞机制[J]．神经解剖学杂志，2004，20（5）：521-524.
[107]张军．全麻药突触前作用机制的研究进展[J]．《国外医学》麻醉学与复苏分册，2003，24（4）：226-229.
[108] Vacher CM，Hardin PH， Steinbusch HW，et al. The effects of nitric oxide on magnocellularneurons could involve multiple indirect cyclic cGMP-dependent pathways[J]. EuropeanJournal of Neuroscience，2003，17：455-466.
[109] Madhusoodanan KS，Ferid M. NO-cGMP signaling and regenerative medicine involvingstem cells[J]. Neurochemical Research，2007，32：681-694.
[110] Jaffrey SR，Erdjument BH，Ferris CD，et al. Protein S-nitrosyla-tion: a physiological signalfor neuronal nitric oxide[J]. Nat Cell Biol，2001，3：193-197.
[111] Adachi T，Kurata J，Nakao S，et al. Nitric oxide synthase inhibitor does not reduce minimumalveolar concentration of halothane in rats[J]. Anesth Analg，1994，78：1154-1157.
[112] Sakai H，Sheng H，Yates RB，et al. Isoflurane provides long-term protection against focalcerebral ischemia in the rat. Anesthesiology，2007，106（1）：92-99.
[113] Nelson LE，Guo TZ，Lu J，et al. The sedative component of anesthesia is mediated byGABA（A） receptors in an endogenous sleep pathway. Nat Neurosci，2002，5（10）：979–84.
[114] Ging Kuo Wang，Corinna Russell，Sho-Ya Wang. State-dependent block of voltage-gatedNa+channels by amitriptyline via the local anesthetic receptor and its implication forneuropathic pain[J]. Pain，2004，11（1-2）：166-174.
[115] Ruth L，Michele C，Patrice G. Atipamezole-precipitated clonidine withdrawal induces c-Fosexpression in rat central nervous system[J]. Brain Research，1997，764(1-2)：81-92.
[116] Hall LW，Clarke KW，Trim CM. Principles of sedation，analgesia and premedication [J].Veterinary anaesthesia，2001，10：90-91.
[117]刘俊杰，赵俊.现代麻醉学[M].第2版.北京：人民卫生出版社，1997，314.
[118]陈新谦，金有豫，汤光，等.新编药物学[M].第15版.北京：人民卫生出版社，2003，222-794.
[119] Ewing KK，Mohammed HO，Scarlett JM，et al. Reduction of isoflurane anestheticrequirement by medetomidine and its restoration by atipamezole in dogs[J]. Am J Vet Res，1993，54：294-299.
[120] Miller M，Weber M，Neiffer D，et al. Anaesthetic induction of captive tigers （Pantheratigris） using a Medetomidine-ketamine combination[J]. J Zoo Wildl Med，2003，34：307-308.
[121] Jacquier M，Aarhaug P，Arnemo JM，et al. Reversible immobilization of free-rangingAfrican lions （Pantheraleo） with medetomidine-tiletamine-zolazepam and atipamezole[J].J Wildl-Dis，2006，42：432-436.
[122] Riekkinen PJ， Sirvi J， Valjakka A， et al. Effects of atipamezole andtetrahydroamino-acridine on nucleus basalis lesion-induced EEG changes[J]. Brain Res Bull，1991，27：231-235.
[123] Ylinen A，Pitk nen M，Pussinen R，et al. A selective antagonists of alpha-2adreno-ceptors，facilitates the excitability of the dentate gyrus and improves the retention of the radial armmaze[J]. Soc Neurosci Abstr，1996，22：680.
[124] David B. Adrenergic Receptors Historical Perspectives From the20th Century[J]. TheReceptors，2006，I：3-21.
[125]庄心良，曾因明，陈伯銮.现代麻醉学[M].第3版.北京：人民卫生出版社，2003，411-412.
[126] James D，WatsonT A，Baker，et al. Molecular Biology of the Gene[M]. BenjaminCummings Publ，2003，752.
[127]王雪.神经细胞的生理和病理过程与原癌基因c-fos的关系[J].国外医学生理病理科学与临床分册，1998，18（4）：358-360.
[128]谢兴国，蔡文琴，张吉强，等.一氧化氮合酶阳性神经元在小鼠脑内的分布[J].解剖学杂志，2002，25（1）：34-51.
[129]余奕军. C-fos技术在全麻机制研究中的应用[J].国外医学麻醉与复苏分册，1998，19（6）：321-322.
[130] Adam S，Hamlin，Gavan P，et a1. Induction of Fos proteins in regions of the nucleusaccumbens and ventrolateral striatum correlates with catalepsy and stereotypic behavioursinduced by morphine[J]. Neuropharmacology，2009，56(4)：798-807．
[131]马加海，徐礼鲜.安氟醚麻醉诱导Fos蛋白与脑啡呔在大鼠中枢神经系统的表达及定位研究[J].中华麻醉学杂志，2001，21（6）：363-365．
[132] Nakao S，Nagata A，Miyamoto E，et a1. Inhibitory effect of propofol on ketamine-inducedc-Fos expression in the rat posterior cingulate and retrosplenial cortices is mediated byGABAA receptor activation[J]. Acta Anaesthesiol Scand，2003，47(3)：284-290．
[133] Nakao S，Adachi T，Murakawa M，et al. Halothane and diazepam inhibit ketamin inducedc-fos expression in the rat cigulate cortex[J]. Anes-thesiology，1996，85(4)：874-882．
[134]徐礼鲜，傅荣国，张惠等.硫贲妥钠诱导c-fos基因在中枢神经系统的表达[J].中国药理学通报，2000，16（3）：271-273．
[135] Kate L，John M. Recent Advances in the Understanding of Genetic Susceptibility to ChronicPain and Somatic Symptoms[J]. Current Rheumatology Reports，2011，13(6)：521-527.
[136]许建阳，王发强，刘庆安.原癌基因c-fos在痛觉调制的研究进展[J].医学综述，2001，10（8）：581-584.
[137] Tateyama S，Ikeda T，Kosai K，et a1. Endomorphins suppress nociception induced c-Fos andZif／268expression in the rat spinal dorsal horn[J]. Eur J Pharmacol，2002，451（1）：79-87.
[138]许霁虹，王多友，张铁铮，等.异丙酚对应激大鼠脑组织不同区域c-fos mRNA表达的影响[J].中华麻醉学杂志，2001，21（11）：679-681.
[139] Shii-Yi Yang，Chen-Jee Hong，Yn-Ho Huang，et al. The effects of glycine transporter Iinhibitor，N-methylglycine （sarcosine），on ketamine-induced alterations in sensorimotorgating and regional brain c-Fos expression in rats [J]. Neuroscience Letters，2010，469(1)：127-130.
[140]刘玉芝，武中林，安海龙，等.离子通道研究新动向[J].河北师范大学学报，2010，34（6）：719-725.
[141]韩贻仁.分子细胞生物学[M].第2版.北京：科学出版社，2001，234-235.
[142]孙大业，郭艳林，马力耕，等编著.细胞信号转导[M].北京：科学出版社，2001,110-103.
[143]徐文洪.离子通道的调控和受体依赖的离子通道研究进展[J].中国药理学通报，1997，13（5）：401-404.
[144] Carme S，Sonia B，Josep M. The Ca2+/calmodulin system in neuronal hyper excitability [J].The International Journal of Biochemistry&Cell Biology，2001，33：439-455.
[145] Krnlevic K， Puil E. Halothane suppresses slow inward currents in hippocampalslices[J].Can J Physiol Pharmacol，1988，66：1570-1575.
[148] Ries CR， Puil E. Isoflurane prevents transitions to tonic and burst firing modes in thalamicneurons[J]. Neurosci. Lett，1993，159：91-94.
[146]周志强，程璐，杨建军，等. DNA微阵列检测异氟醚麻醉的基因表达[J].临床麻醉学杂志，2006，22（5）：369-371.
[147] Lihui Yan，MD，Xiaojing Jiang，MD，PhD，Wenjun Tai，MD，et al. Emulsified isofluraneinduces postconditioning against myocardial infarction via JAK-STAT pathway[J]. journal ofsurgical research，2012，178：578-585.
[148] Lei Zhang，Nanfu Luo，Jin Liu，et al. Emulsified Isoflurane Preconditioning ProtectsAgainst Liver and Lung Injury in Rat Model of Hemorrhagic Shock[J]. Journal of SurgicalResearch，2011，171：783-790.
[149]易传安，何绘敏，胡祥上，等. NMDA受体NR1、NR2A/B在丘脑前核-海马CA1、CA3脑区和齿状回的分布与表达[J].中国老年学杂志，2011，31（7）：1152-1155.
[150] Masatou K，Kazuyoshi H，Mihoko K，et al． Inhibitory effects of intravenous anaestheticagents on K+evoked glutamate release from rat cerebroeortical sliees： involvement ofvoltage-sensitive Ca2+channels and GABAAreceptors [J]．Naunyn Sehmiedeberg’s-Archpharmacol，2002，366：246-253.
[151] Takashi K. Functional roles of ATP-sensitive potassium channel as related to anesthesia[J].Journal of Anesthesia，2012，26(1)：152-155.
[152] Yost CS. Baseline K+channels as targets of general anesthesties：studies of the action ofvolatile anesthetics on TOKI[J]. Toxicol-Lett，1998，100：101-103.
[153] María S，Blanca IA，Luz M，et al.Characterization of Phenytoin，Carbamazepine，Vinpocetine and Clorgyline Simultaneous Effects on Sodium Channels and CatecholamineMetabolism in Rat Striatal Nerve Endings Glu and Asp release was unchangeds[J].Neurochemical Research，2009，34(3)：470-479.
[154]范宏刚.小型猪复合麻醉剂的研制及其全麻机理的研究[D].东北农业大学博士学位论文，2008，82-110.
[155]卢静，戴体俊，曾因明，等.短时吸入安氟醚、异氟醚对大鼠边缘系统c-fos基因表达的影响[J].中国药理学通报，2004，20（3）：259-261.
[156] Parekh AB and Putney JW. Store operated calcium channel[J]. Physiol Rev，2005，85(2)：777-792.
[157] Li Z，Lu J，Xu P，et al. Mapping the Interacting Domains of STIM1and Orai1in Ca2+Release activated Ca2+Channel Activation[J]. J Biol Chem，2007，282(40)：29448-29456.
[158]谢玉波，徐林，刘敬臣. γ-氨基丁酸受体和甘氨酸受体在大鼠丙泊酚麻醉中的作用[J].临床麻醉学杂志，2006，22(9)：691-693.
[159]王晟，刘明政，刘进.30%脂肪乳剂对异氟醚血/气分配系数的影响[J].临床麻醉学杂志，2003，19（2）：87-88.
[160]杨孟昌，陈玉培，张文，等. ATP敏感性钾通道在乳化异氟醚心肌保护效应中的作用[J].中国药理学通报，2009，25（2）：169-172.
[161] Nishizawa N，Nakao S，Nagata A，et al. The effect of ketamine isomers on both micebehavioral responses and c-fos expression in the Posterior cingulated and retrospleniacortices[J]. Brain Res，2000，857：188-192.
[162]屈强，史忠，杨天德. c-fos原癌基因的表达与全身麻醉[J].医学综述，2004，10（12）：743-746.
[163] Rajadhyaksha A，Barczak A，Macias W，et al. L-type Ca2+channels are essential forglutamate-mediated CREB phosphorylation and c-fos gene expression in striatal neurons[J]. JNeurosci，1999，19：6348-6359.
[164] Lerea LS，Butler LS，McNamara J O. NMDA and non-NMDA receptor-mediated increase ofc-fos mRNA in dentate gyrus neurons involves calcium influx via different routes[J]. J.Neurosci，1992，12：2973-2981.
[165] Hyun L，Hyun P. Matrix metalloproteinase-13expression in IL-1β-treated chondrocytes byactivation of the p38MAPK/c-Fos/AP-1and JAK/STAT pathways[J]. Archives of PharmacalResearch，2011，34(1)：109-117.
[166] Francisco EM， álvarez T. Oxidative defence reactions in sunflower roots induced bymethyl-jasmonate and methyl-salicylate and their relation with calcium signalling InmaculadaGarrido [J]. Protoplasma，2009，237(1-4)：27-39.
[167] Ping Liao，Heng Yu Zhang，Tuck W. Alternative splicing of voltage-gated calciumchannels： from molecular biology to disease[J]. Pflügers Archiv European Journal ofPhysiology，2009，458(3)：481-487.
[168]文欣荣. c-fos与c-jun基因在异丙酚麻醉下大鼠中枢神经核团分布的研究[D].第三军医大学硕士学位论文，2004，5，1397-1399.
[169]阳敏燕，综述，孙红斌.即刻早期基因c-fos、谷氨酸受体与癫痫的研究进展[J].实用医院临床杂志，2009，11（6）：122-127.
[170]马晓旭，戴体俊，曾因明. NO/cGMP信号转导系统与氯胺酮麻醉[J].《国外医学》麻醉学与复苏分册，2004，25（4）：206-208.
[171] RAO Yan，WANG Yan-lin，CHEN Yong-quan. Protective effects of emulsified isofluraneafter myocardial ischemia-reperfusion injury and its mechanism in rabbits[J]. ChineseJournal of Traumatology，2009，12（1）：18-21.
[172] Claudia Spadavecchia，Olivier Levionnois，Peter Kronen，et al. The effects of isofluraneminimum alveolar concentration on withdrawal reflex activity evoked by repeatedtranscutaneous electrical stimulation in ponies[J]. The Veterinary Journal，2010，183(37)337-344.
[173] Johnson C，Hill C，Chawala S，et al. Calcium controls gene expression via three distinctpathways that can function independently of the ras/mitogen-activated protein kinases（ERKs） signaling cascade[J]. J Neurosci，1997，17：6189-6202.
[174] Smyth JT，Dehaven WI，Jons BF，et al. Emerging perspectives in store operated Ca2+entry：roles of Orai，St im and TRP[J]. Bio ch m Biophys Acta，2006，1763（11）：1147-1160.
[175]赵利华，韦良玉，陈煌.艾灸对D-半乳糖衰老小鼠学习记忆、大脑组织NOS/NO-cGMP信号系统及c-fos mRNA的影响[J].上海针灸杂志，2012，31（3）：194-197.
[176]苗青，缪雪蓉，陆智杰，等.丙泊酚对大鼠的空间学习记忆和海马NMDA受体NR2A亚基表达的影响[J].临床军医杂志，2010，38（3）：330-334.
[177] Masatou K，Kazuyoshi H，Mihoko K，et al． Inhibitory effects of intravenous anaestheticagents on K+-evoked glutamate release from rat cerebroeortical sliees： involvement ofvoltage-sensitive Ca2+channels and GABAAreceptors[J]． Naunyn Sehmiedeberg’s-Archpharmacol，2002，366：246-253.
[178] Takashi K. Functional roles of ATP-sensitive potassium channel as related to anesthesia[J].Journal of Anesthesia，2012，26(1)：152-155.
[179] María S，Blanca IA，Luz M，Vladimir Nk.Characterization of Phenytoin，Carbamazepine，Vinpocetine and Clorgyline Simultaneous Effects on Sodium Channels and CatecholamineMetabolism in Rat Striatal Nerve Endings Glu and Asp release was unchangeds[J].Neurochemical Research，2009，34(3)：470-479.
[180]王恒林，米卫东，王卓强，等.丙泊酚对匹鲁卡品诱发癫痫持续状态大鼠海马NMDA受体2A、2B亚型表达的影响[J].解放军医学杂志，2010，35（5）：530-533.
[181]孙大业，郭艳林，马力耕，等编著.细胞信号转导[M].北京：科学出版社，2001.
[182] Sato J，Saito S，Jonokoshe H，et al. Correlation and linear regression between blood pressuredecreases after a test dose injection of propofol and that following anaesthesia induction[J].Anaesth Intensive Care，2003，31(5)：523.
[183] Lee J， Rushlow W. L-type calcium channel blockade on haloperidol-induced c-Fosexpression in the striatum[J]. Neuroscience，2007，149：602-616.
[184] Barro′n S，Tusell J M，Sola`C，et al. Convulsant agents activate c-fos induction in both acalmodulin-dependent and calmodulin-independent manner[J]. J. Neurochem，1995，65(a)：1731-1739.
[185]詹纯列，徐本法，白朝晖.小型猪在医学实验中的应用[J].中国实验动物学杂志，2010，10（2）：118-120.
[186]张德福，刘东.国内外小型猪实验动物化研究[J].生物学学报，2004，39（10）：14-16.
[187] Tadahito H，Hirotaka T，Takafumi M，et al. Alterations in NMDA Receptor Subunit Levelsin the Brain Regions of Rats Chronically Administered Typical or Atypical AntipsychoticDrugs [J]. Neurochemical Research，2003,28(6)：919-924.
[188]卢德章，范宏刚，于世明，等.替来他明诱导大鼠中枢神经系统c-fos基因的表达[J].畜牧兽医学报，2010，41（7）：878-882.
[189] Ferguson H A，Goodrich J A. Expression and purification of recombinant human c-fos、c-junthat is highly active in DNA binding and transcriptional activation in vitro[J]. Nucleic AcidsRes，2001，29(20)：98-101.
[190] Hsieh CL,Lin JJ,Chiang SY,et al. Gastrodia elata modulated activator protein1via c-JunN-terminal kinase signaling pathway in kainic acid-induced epilepsy in rats[J].JEthnopharmacol，2007，109(2)：241-247.
[191]许霁虹，张铁铮，刘晓江，等.氯胺酮麻醉引起c-fos基因在大鼠大脑皮质的表达[J].临床麻醉学杂志，2005，21（2）：116-117.
[192] Jansson A，Olin K，Yoshitake T，et al. Effects of isoflurane on prefrontal acetylcholinerelease and hypothalamic Fos response in young adult and aged rats[J]. ExperimentalNeurology，2004，190：535–543.
[193]陈功，江澄川. C-fos、c-jun与癫痫[J].中华神经医学杂志，2005，4（8）：853-854.
[194] Kovacs K J. Measurement of immediate-early gene activation c-fos and beyond[J].Neuroendocrinol，2008，20：665-672.
[195] Makoto K， Todd A， Chunmei Y， et al. Neurotransmitter regulation of c-fos andvasopressin gene expression in the rat supraoptic nucleus[J]. Experimental Neurology，2009，219：212-222.
[196]胡云,杨京利,王燕.异氟醚麻醉大鼠脊髓NOS活性和NO产量的动态变化[J].郧阳医学院学报，2004，23（4）：211.
[197] Angel B，Hélène M. Genetic Approaches to Investigate the Role of CREB in NeuronalPlasticity and Memory[J]. Molecular Neurobiology，2011，44(3)：335-332.
[198] Kate L, John M. Recent Advances in the Understanding of Genetic Susceptibility toChronic Pain and Somatic Symptoms[J]. Current Rheumatology Reports，2011，13(6)：521-527.
[199]谢兴国，蔡文琴，张吉强，等.一氧化氮合酶阳性神经元在小鼠脑内的分布[J].解剖学杂志，2002，25（1）：34-51.
[200]徐铁军，樊红彬，张凤真，等. NMDA受体亚单位NR1、NR2A和NR2B在大鼠海马的免疫组织化学表达[J].解剖学杂志，2002，25（2）：128-131.
[201]张志龙，费剑春，段世明. NMDA受体与氮胺酮麻醉[J].《国外医学》麻醉学与复苏分册，2000，21（1）：13-15.
[202] Lana J，Mawhinney, Ofelia F，et al. Isoflurane/nitrous oxide anesthesia induces increases inNMDA receptor subunit NR2B protein expression in the aged rat brain[J]. Brain Research，2012，14（31）：27-29.
[203]杜玉玲.丙泊酚和异氟醚复合麻醉在颅脑外科手术中的应用[J].中国校医，2007，21（5）：577.
[204]梁效安，郭晓文，胡建英，等.不同种类的局麻药硬膜外麻醉复合吸入麻醉对异氟醚MAC值的影响[J].医学研究杂志，2007，36（5）：100-101.
[205]宋乐，朱正华，张西京，等.大鼠腹腔内注射异氟醚麻醉效应的初步研究[J].临床麻醉学杂志，2007，23（8）：661-663.
[206] Bjorkblom B，Ostman N，Hongisto V，et al. Constitutively active cytoplasmic c-Jun N-terminal kinase1is a dominant regulator of dendritic architecture：role of microtubule associatedprotein2as an effector[J]. J Neurosci，2005，25(27)：6350-6361.
[207] Chih-Hung Lee, Chang Zhu, John Malysz, et al. α4β2neuronal nicotinic receptor positiveallosteric modulation: An approach for improving the therapeutic index of α4β2nAChRagonists in pain[J].Biochemical Pharmacology，2011，82（8）：959-966.
[208] Tanxing Cui，Christian G，Canlas，et al. Anesthetic effects on the structure and dynamics ofthe second transmembrane domains of nAChR α4β2[J]. Biochimica et Biophysica Acta，2010，1978（2）：161-166.
[209]史宝林，周少朋，崔云峰.地氟醚和异氟醚对脑电图的影响[J].黑龙江医学，2003，27（6）：417-419.
[210] Vasyl Bondarenko， David Mowrey， Lu Tian Liu，et al. NMR resolved multiple anestheticbinding sites in the TM domains of the α4β2nAChR[J]. Biochimica et Biophysica Acta，2013，1828（2）：398-404.
[211]杨经文，易明量，柴云飞，等.芬太尼对乳化异氟醚催眠作用的影响[J].四川大学学报，2007，38（6）：973-976.
[212] James D，WatsonT A，Baker，et al. Molecular Biology of the Gene[M]. BenjaminCummings Publ，2003，752.
[213]尹宁.丙泊酚、咪吐安定对大鼠心肌缺血再灌注损伤Fos、Jun蛋白表达的影响[D].南京医科大学硕士学位论文，2005，6-38.
[214] Hyun L，Hyun P. Matrix metalloproteinase-13expression in IL-1β-treated chondrocytes byactivation of the p38MAPK/c-Fos/AP-1and JAK/STAT pathways[J]. Archives of PharmacalResearch，2011，34(1)：109-117.
[215] Nakao S，Nagata A，Miyamoto E，et a1. Inhibitory effect of propofol on ketamine-inducedc-Fos expression in the rat posterior cingulate and retrosplenial cortices is mediated byGABAA receptor activation[J]. Acta Anaesthesiol Scand，2003，47(3)：284-290.
[216]卢德章，范宏刚，于世明，等.隆朋对替来他明/唑拉西泮诱导的大鼠不同脑区c-fos基因表达的影响[J].中国兽医杂志，2011，47（6）：23-25.
[217]许霁虹，王多友，张铁铮，等.异丙酚对应激大鼠脑组织不同区域c-fos mRNA表达的影响[J].中华麻醉学杂志，2001，21（11）：679-681.
[218] Shii-Yi Yang，Chen-Jee Hong，Yn-Ho Huang，et al. The effects of glycine transporter Iinhibitor，N-methylglycine （sarcosine），on ketamine-induced alterations in sensorimotorgating and regional brain c-Fos expression in rats [J]. Neuroscience Letters，2010，469(1)：127-130.
[219]刘玉芝，武中林，安海龙，等.离子通道研究新动向[J].河北师范大学学报，2010，34（6）：719-725.
[220]韩贻仁.分子细胞生物学[M].第2版.北京：科学出版社，2001，234-235.
[221]李文波.七氟醚麻醉对脑c-jun水平的影响[D].吉林大学硕士学位论文，2011，6-19.
[222] Sato J，Saito S，Jonokoshe H，et al. Correlation and linear regression between blood pressuredecreases after a test dose injection of propofol and that following anaesthesia induction[J].Anaesth Intensive Care，2003，31(5)：523.