胃电刺激对药物诱导的犬呕吐症状和胃肌电活动的影响及其中枢机制研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
第一部分顺铂和阿朴吗啡对犬呕吐症状和胃慢波的影响
     目的观察分别给予顺铂(Cisplatin)和阿朴吗啡(Apomorphine)后犬呕吐等消化不良症状的程度及其对胃肌电活动的影响。
     方法7只比格犬分别植入4对胃浆膜电极,并进行2部分实验。1.顺铂组:每只犬分别记录给药前20min胃电基线水平及消化不良症状后,经静脉持续注射顺铂溶液(1.5 mg/kg溶于250 ml生理盐水)1h,并自实验开始持续记录胃肌电活动及动物症状共约6 h。2.阿朴吗啡组:将阿朴吗啡0.1mg/kg溶于生理盐水中配成0.01 mg/ml溶液,记录给药前胃电图基线水平15 min后皮下注射阿朴吗啡,以15 min为时间段,连续记录胃电活动和动物症状45 min。
     结果1.顺铂和阿朴吗啡均能诱导犬恶心呕吐等消化不良症状。(1)比格犬静脉注射顺铂期间及之后的约2.5 h内症状较轻微,其症状评分分别为1.86±0.26和7.43±1.39;在给药停止后约3 h动物开始出现频繁舔舌、哈欠、闭眼、急促呼吸等恶心样症状及呕吐,呕吐期间症状评分为20.29±0.94,较给药开始时明显增加(P<0.01),平均呕吐次数为5.0±1.86次;呕吐停止后动物症状逐渐恢复,症状评分为2.86±0.4。(2)阿朴吗啡组动物呕吐次数为5.29±0.87次,呕吐期间症状评分为12±0.95,之后逐渐降低至2.00±0.62。2.通过胃电记录发现,顺铂组给药前正常胃慢波占(89.7±3.11)%,而呕吐期间正常胃慢波为(67.0±5.1)%(P<0.001),并且胃电过速和胃电过缓发生的百分比明显高于给药前水平(P=0.008和P=0.026),此外,顺铂还能减少胃慢波的主功率。在给药前胃慢波主功率为(1.5±2.1)dB,在呕吐期间主功率减低至(-3.3±0.7) dB (P=0.038)。阿朴吗啡组在呕吐期间其正常胃慢波百分比则从给药前的(96.51±1.14)%降低至(53.07±6.72)%,并且该时间段胃电过速和胃电过缓发生的比例同样高于给药前水平(P=0.011和P=0.015)。而胃电主频率及主功率并无明显变化。
     结论顺铂和阿朴吗啡均能诱导犬呕吐和恶心样症状,并引起胃电紊乱。
     第二部分胃电刺激对阿朴吗啡和顺铂诱导的犬呕吐症状的影响
     目的研究阿朴吗啡(Apomorphine,APO)和顺铂(Cisplatin,DDP)对胃肌电活动的影响,并探讨胃电刺激(Gastric Electrical Stimulation,GES)对化疗药物引起的犬呕吐和消化不良症状的治疗效应。
     方法7只比格犬分别植入4对胃浆膜电极,每只犬分别进行2部分实验。1.阿朴吗啡组:(1)对照组(APO-C):记录给药前胃电图基线水平15 min后皮下注射阿朴吗啡(0.1 mg/kg),以15 min为时间段,连续记录胃电活动和动物症状60 min。(2)阿朴吗啡+电刺激组(APO+GES):每只犬均进行4次实验。每次实验给药及记录方法同对照组,但在阿朴吗啡给药的同时经近端胃体电极分别给予不同参数胃电刺激,并持续至实验结束,根据4组参数的结果选出一组最佳参数,并用于顺铂部分的实验。2.顺铂组:(1)DDP对照组在记录20 min胃慢波基线及动物症状后,持续静脉注射DDP溶液(1.5 mg/kg溶于250 ml生理盐水)1 h,在给药期间及给药后的5 h内持续记录胃电活动及动物症状,并计算症状评分;(2)DDP+GES组除了在给药同时开始经近端胃体部电极持续给予GES外,其给药方式、剂量及胃电和症状记录同各自的对照组。
     结果1.阿朴吗啡和顺铂均能诱导犬恶心呕吐等症状及胃电紊乱。(1)APO对照组动物平均呕吐次数为5.29±0.87次,总症状评分为20.57±1.81。呕吐期间其正常胃慢波仅为(53.07±6.72)%,并且该时间段胃电过速和胃电过缓发生的比例同样高于基线水平(P=0.011和P=0.015)。(2)DDP对照组动物均出现频繁呕吐,平均呕吐次数为5.5±1.2次,总症状评分为31.83±2.75。通过胃电记录发现,给药前基线水平正常胃慢波占(96.5±1.14)%,而呕吐期间正常胃慢波降低至(69.61±5.81)%(P=0.003vs.baseline),并且胃电过速和胃电过缓发生的百分比均明显高于给药前水平(P=0.02和P=0.031)。2.胃电刺激能减轻阿朴吗啡和顺铂诱导的呕吐和消化不良症状。(1)4组胃电刺激参数中GES4能显著改善APO诱导的呕吐反应。APO+GES4组动物呕吐次数明显减少(3.71±0.61,P=0.025 vs.APO对照组),其症状评分降低至15.86±1.82(P=0.033 vs.对照组)。(2)DDP+GES组动物的症状评分也较对照组明显降低(24.5±1.45,P=0.028),并且呕吐次数也明显减少(3.67±0.8,P=0.028)。但胃电刺激对两种药物引起的胃电紊乱并无明显影响。
     结论阿朴吗啡和顺铂能诱导犬呕吐和胃电紊乱。高频串脉冲胃电刺激能明显减轻药物引起的呕吐和消化不良症状,但对胃电变化无明显影响。
     第三部分胃电刺激的脑功能磁共振研究
     目的研究不同参数的胃电刺激对犬中枢神经系统神经元活性的影响,初步探讨胃电刺激的中枢作用机制。
     方法5只比格犬只分别植入4对胃浆膜电极。每只犬于麻醉后分别给予3种不同参数的胃电刺激(串脉冲、短脉冲和长脉冲),并进行fMRI扫描。fMRI扫描共分2部分:扫描犬静息状态下脑血流情况(5 min),随即持续给予不同参数的胃电刺激15min,比较胃电刺激前后脑血流变化。
     结果串脉冲组在给予胃电刺激后脑血流信号明显增强的区域主要为海马、杏仁核、额叶、枕叶及脑干。部分犬在后丘脑(外侧膝状体、内侧膝状体)、腹侧丘脑和嗅回区域也可检测到血流信号的增强。短脉冲与长脉冲组血流信号明显增强的区域主要为脑干、额叶和枕叶,而海马和/或杏仁核区域均未见活化信号(P=0.038 vs.串脉冲组,卡方检验)。此外,短脉冲组在小脑区域可见明显的活化信号(P=0.039 vs.串脉冲组),而长脉冲组小脑区域活化信号较弱。
     结论3种参数的胃电刺激均可引起脑干区域活化,提示脑干核团可能是3种刺激参数共同的作用通路。串脉冲和短脉冲刺激还可引起与内脏感觉相关的中枢区域活化,长脉冲刺激则对内脏感觉相关区域无明显作用。
Part 1 Drug-Induced Gastric Dysrhythmia and Emesis in Dogs
     Aims: The aims of this study were to investigate the effects of Cisplatin (DDP) andApomorphine (APO) on gastric myoelectrical activity in dogs.
     Methods: Seven female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a two-session study.Intravenous infusion of DDP (1.5 mg / kg)was given for 1h in DDP session.APO (0.1 mg/kg) was injected subcutaneously in APOsession.Gastric slow waves and emesis as well as behaviors suggestive of nausea wererecorded in each session.
     Results: 1.DDP and APO induced emesis and behaviors suggestive of nausea.(1) TheEmesis frequency was 5.5±1.2 in DDP session.The symptoms were slight in the period ofinfusion and before vomiting, and the symptoms scores were 1.86±0.26 and 7.43±1.39.Allthe dogs presented more frequent nausea-like responses such as licking tongue, belchingand chasma, and multiple vomiting.The behavioral score in the vomiting period was20.3±0.9, which was higher than that in other periods (each P < 0.01).(2) In the APOsession, the vomiting frequency was 5.29±0.87.All the dogs presented more frequentnausea-like responses within 15min after APO infusion, and the symptoms score in thisperiod was 12±0.95 (P < 0.001 vs.baseline).Within 30 - 45 min after APO infusion, thesymptoms score decreased to 2.00±0.62 (P=0.085 vs.baseline).2.DDP and APO inducedgastric dysrhythmia.(1) In DDP session, the percentage of normal slow waves decreasedsignificantly during the 2.5 h before vomiting ((77.7±5.6) %, P=0.01 ) and the period ofvomiting ((69.8±4.5) %, P < 0.001) compared with baseline.In addition, the dominantpower of gastric slow wave decreased from (1.5±2.1) dB in baseline to (-3.3±0.7) dB in the period of vomiting (P=0.038).(2) It also induced bradygastria and tachygastria in thefirst 15min after APO infusion (P=0.015 and P=0.011 vs.baseline).The normal slowwave was (53.07±6.72) % (P=0.001 vs.baseline).
     Conclusion: Cisplatin and Apomorphine induced emesis and nausea-like responses,which caused gastric dysrhythmia.
     Part 2 Effect of Gastric Electrical Stimulationon Drug-Induced Emesis
     Objective The aims of this study were to investigate the effects of Cisplatin (DDP)and Apomorphine (APO) on gastric myoelectrical activity and the roles of GES in treatingdrug-induced emesis in dogs.
     Methods Seven female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a two -session study.1.APO (0.1 mg/kg) was injectedsubcutaneously in APO-control session and APO + GES session.4 kinds of GES wereapplied on the proximal pair of gastric electrodes from drugs infusion in APO-GESsessions.Select the best parameter according to the result and apply it to the DDP-GESsession.2.Intravenous infusion of DDP (1.5 mg/kg) was given for 1h in DDP -controlsession and DDP + GES session.It lasted 6 h in GES session and 1 h in APO + GESsession.Gastric slow waves and animal behaviors were recorded in each session.
     Results 1.Cisplatin and Apomorphine induced emesis and behaviors suggestive ofnausea, and gastric dysrhythmia.(1) The total number of emesis was 5.5±1.2 in DDP-control session, and thc total symptom score was 31.83±2.75.The gastric slow waveshowed both bradygastria and tachygastria during the period of emesis (P=0.031 and P=0.02 vs.baseline).The percentage of normal slow wave was 69.61±5.81% during thisperiod (P=0.003 vs.baseline).(2) In the APO -control session, the total number of emesiswas 5.29±0.87 and the symptom score was 20.57±1.81.It also induced bradygastria andtachygastria in the first 15 min after APO infusion (P=0.015 and 0.011 vs.baseline).Thenormal slow wave was (53.07±6.72) % (P=0.001 vs.baseline).2.GES reduced emesisand the animal behavioral score suggestive of nausea compared with control sessions.(1)Among these 4 parameters, GES4 can reduced the vomiting time significantly.The totalsymptoms score in APO + GES4 session decreased (15.86±1.82, P=0.033 vs.controlsession).GES4 can also decrease the vomiting time in this session (3.71±0.61, P=0.025vs.control session).(2) The total symptom score in DDP + GES session decreased to 24.5±1.45 (P=0.028 vs.control session), and the vomiting times was 3.67±0.8(P=0.028vs.control session).However, GES had no effects on gastric dysrhythmia.
     Conclusion APO and DDP induced emesis and gastric dysrhythmia.GES with trainsof short pulses relieves drug -induced emetic responses but has no effects on dysrhythmia.
     Part 3 Functional Magnetic Resonance Imaging on GastricElectrical Stimulation in Dogs
     Objective To investigate the effect of gastric electrical stimulation (GES) withdifferent parameters on the neuronal activity in central nervous system, and find thepossible mechanism of GES.
     Methods Five female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a three - part study.Each dog was anesthetized and given 3kinds of GES (trains of short pulse, shout pulse and long pulse) for 15min after baseline (5min) respectively.The location of cerebral activation induced by GES was investigated byfMRI.
     Result fMRI showed that GES with trains of short pulse induced BOLD - signalincreased in brainstem, frontal lobe, occipital lobe, and limbic brain areas, including theamygdale and hippocampus, which were considered to be correlated with chemoreceptortrigger zone and visceral sensation.GES with short pulse induced signal increased inbrainstem, occipital lobe, frontal lobe and cerebellum, but GES with long pulse only causedneuron activity in brainstem, frontal lobe and occipital lobe.
     Conclusion Each of these GES caused BOLD - signal increased in brainstem, whichindicate that the brainstem may be the same original pathway in the effect of GES oncentral nervous system.GES with short pulse and trains of short pulse also caused neuronalactivity in the areas correlated with visceral sensation.However, GES with long pulse hadno effect on the visceral sensation correlated areas.
引文
1. Khan NU, Razzak JA. Abdominal pain with rigidity secondary to the anti-emetic drug metoclopramide. J Emerg Med, 2006, 30: 411-413.
    2. Ritter MJ, Goodman BP, Sprung J, et al. Ondansetron-induced multifocal encephal-opathy. Mayo Clin Proc, 2003, 78: 1150-1152.
    3. Chen JD, Richards RD, McCallum RW. Identification of gastric contractions from the cutaneous electrogastrogram. Am J Gastroenterol,1994,89: 79-85.
    4. Qian LW, Pasricha J, Chen JDZ. Origins and patterns of spontaneous and drug-induced canine gastric myoelectrical dysrhythmias. Dig Dis Sci,2003,48: 508-515.
    5. Borison HL, Borison R, McCarthy LE. Role of the area postrema in vomiting and related functions. Fed Proc, . 1984, 43 (15): 2955 -2958.
    6. Miller AD ,Nonaka S ,Jakus J . Brain areas essential or non-essential for emesis. Brain Res, 1994, 647: 255 -264.
    7. Hornby PJ. Central neurocircuitry associated with emesis. Am J Med, 2001,111 Suppl 8A: 106S-112S
    8. Harding RK, Hugenholtz H, Keaney M, Kucharczyk J. Discrete lesions of the area postrema abolish radiation-induced emesis in the dog. Neurosci Lett, 1985, 53 (1): 95-100.
    9. Darmani NA, Wang Y, Abad J, et al. Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists. Brain Res, 2008, 1214: 58-72.
    10. Saito R, Takano Y, Kamiya HO. Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. J Pharmacol Sci, 2003, 91 (2): 87-94.
    11. Wuchert F, Ott D, Rafalzik S, et al. Tumor necrosis factor-alpha, interleukin -lbeta and nitric oxide induce calcium transients in distinct populations of cells cultured from the rat area postrema. J Neuroimmunol, 2009, 206 (1-2): 44-51.
    12. Horn CC, Richardson EJ, Andrews PL, et al. Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin. Auton Neurosci, 2004, 115 (1-2): 74-81.
    13. Maolood N, Meister B. Protein components of the blood-brain barrier (BBB) in the brainstem area postrema-nucleus tractus solitarius region. J Chem Neuroanat. 2009, 37 (3): 182-195.
    14. Miller AD, Leslie RA. The area postrema and vomiting. Front Neuroendocrinol, 1994, 15 (4): 301-320.
    15.王德山,单德红,于化新,等.呕必宁对顺铂所致脑组织5 -HT含量变化的影响.中华中医药学刊,2007,25(5):869-871.
    16. Funahashi M, Mitoh Y, Matsuo R. Activation of presynaptic 5-HT3 receptors facilitates glutamatergic synaptic inputs to area postrema neurons in rat brain slices. Methods Find Exp Clin Pharmacol, 2004, 26 (8): 615 -622.
    17. Chen J, McCallum RW. Gastric slow wave abnormalities in patients with gastroparesis. Am J Gastroenterol, 1992, 87: 477-482.
    18. Smout AJ, van der Schee EJ, Grashuis JL. What is measured in electrogastrography? Dig Dis Sci, 1980, 25: 179-187.
    19. Verghagen MA, Samsom M, Smout JP. Effects of intraduodenal glucose infusion on gastric myoelectrical activity and antropyloroduodenal motility. Am J Physiol, 1998, 274: G1038-1044.
    20. Levanon D, Goss B, Chen JD. Inhibitory effect of white wine on gastric myoelectrical activity and the role of vagal tone. Dig Dis Sci, 2002, 47: 2500-2505.
    21. Chin CL, Fox GB, Hradil VP, et al. Pharmacological MRI in awake rats reveals neural activity in area postrema and nucleus tractus solitarius: relevance as a potential biomarker for detecting drug-induced emesis. Neuroimage. 2006, 33 (4): 1152-1160.
    22. Castro A, Mearin F, Larish J, et al. Gastric fundus relaxation and emetic sequences induced by apomorphine and intragastric lipid infusion in healthy humans. Am J Gastroenterol. 2000, 95 (12): 3404-3411.
    23. Kawachi M, Hori N, Takei M, et al. Gastric relaxation induced by electrical and chemical stimulation of the area postrema in the rat. Gen Physiol Biophys. 2008 , 27 (4): 243-252.
    24. Koga T, Kobashi M, Mizutani M, et al. Area postrema mediates gastric motor response induced by apomorphine in rats. Brain Res. 2003, 960 (1-2): 122-131.
    1. Khan NU, Razzak JA. Abdominal pain with rigidity secondary to the anti-emetic drug metoclopramide. J Emerg Med, 2006, 30: 411-413.
    2. Ritter MJ, Goodman BP, Sprung J, et al. Ondansetron-induced multifocal encephalopathy. Mayo Clin Proc, 2003, 78: 1150-1152.
    3. Chen JD, Richards RD, McCallum RW. Identification of gastric contractions from the cutaneous electrogastrogram. Am J Gastroenterol, 1994, 89: 79-85.
    4. Qian LW, Pasricha J, Chen JDZ. Origins and patterns of spontaneous and drug-induced canine gastric myoelectrical dysrhythmias. Dig Dis Sci, 2003, 48: 508-515.
    5. de Csepel J, Goldfarb B, Shapsis A, et al. Electrical stimulation for gastroparesis. Gastric motility restored, Surg Endosc, 2006, 20:302-306.
    6. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology, 2003,125: 421-428.
    7. Song G, Hou X, Yang B, et al. Two-channel gastric electrical stimulation accelerates delayed gastric emptying induced by vasopressin. Dig Dis Sci, 2005, 50: 662-668.
    8. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology, 2003,125: 421-428.
    9. Hocking MP, Vogel SB, Sninsky CA. Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing. Gastroenterology, 1992, 103: 1811-1816.
    10. Xu X, Qian L, Chen JD. Anti-dysrhythmic effects of long-pulse gastric electrical stimulation in dogs. Digestion, 2004, 69: 63-70.
    11. Lin ZY, McCallum RW, Schirmer BD, Chen JD: Effects of pacing parameters on entrainment of gastric slow waves in patients with gastroparesis. Am J Physiol, 1998, 274: G186-191.
    12. Qian L, Lin X, Chen JD. Normalization of atropine-induced postprandial dysrhythmias with gastric pacing. Am J Physiol, 1999, 276: G387-392.
    13. Chen JD, Qian L, Ouyang H, et al. Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs. Gastroenterology, 2003, 124: 401-409.
    14. de Csepel J, Goldfarb B, Shapsis A, et al. Electrical stimulation for gastroparesis. Gastric motility restored. Surg Endosc, 2006, 20: 302-306.
    15. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology, 2003, 125: 421-428.
    16. Xing JH, Chen JD. Gastric electrical stimulation with parameters for gastroparesis enhances gastric accommodation and alleviates distention-induced symptoms in dogs. Dig Dis Sci, 2006, 51: 2160-2164.
    17. Song G, Hou X, Yang B, et al. Efficacy and efficiency of gastric electrical stimulation with short pulses in the treatment of vasopressin-induced emetic responses in dogs. Neurogastroenterol Motil, 2006, 18: 385-391.
    18. Horn CC, Richardson EJ, Andrews PL, et al. Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin. Auton Neurosci, 2004, 115 (1-2): 74-81.
    19. Maolood N, Meister B. Protein components of the blood-brain barrier (BBB) in the brainstem area postrema-nucleus tractus solitarius region. J Chem Neuroanat. 2009, 37 (3): 182-95.
    20.王德山,单德红,于化新,等.呕必宁对顺铂所致脑组织5-HT含量变化的影响.中华中医药学刊,2007,25(5):869-871.
    21. Chin CL, Fox GB, Hradil VP, et al. Pharmacological MRI in awake rats reveals neural activity in area postrema and nucleus tractus solitarius: relevance as a potential biomarker for detecting drug-induced emesis. Neuroimage. 2006, 33 (4):1152-60.
    22. Zhang X, Fogel R, Renehan WE. Stimulation of the paraventricular nucleus modulates the activity of gut-sensitive neurons in the vagal complex. Am J Physiol. 1999 ;277 (1 Pt 1):G79-90.
    23. Liu J, Qiao X, Chen JD. Vagal afferent is involved in short-pulse gastric electrical stimulation in rats. Dig Dis Sci, 2004, 49: 729-737.
    24. Qin C, Sun Y, Chen JD, et al. Gastric electrical stimulation modulates neuronal activity in nucleus tractus solitarii in rats. Auton Neurosci, 2005,119: 1-8.
    1. Bilgutay AM, Lillehei CW, Wingrove R, et al. Gastrointestinal pacing: a new concept in the treatment of ileus. Biomed Sci Instrum, 1963, 1: 377-383.
    2. Lin ZY, McCallum RW, Schirmer BD, et al. Effects of pacing parameters on entrainment of gastric slow waves in patients with gastroparesis. Am J Physiol, 1998, 274 (1Pt1): G186-191.
    3. Hocking MP, Vogel SB, Sninsky CA.Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing. Gastroenterology, 1992, 103: 1811-1816.
    4. Xu X, Qian L, Chen JD. Anti-dysrhythmic effects of long-pulse gastric electrical stimulation in dogs. Digestion, 2004, 69: 63-70.
    5. Lin ZY, McCallum RW, Schirmer BD, et al. Effects of pacing parameters on entrainment of gastric slow waves in patients with gastroparesis. Am J Physiol, 1998, 274: G186-191.
    6. Song G, Hou X, Yang B,et al. Two-channel gastric electrical stimulation accelerates delayed gastric emptying induced by vasopressin. Dig Dis Sci, 2005, 50: 662-668.
    7. Qian L, Lin X, Chen JD.Normalization of atropine-induced postprandial dysrhythmias with gastric pacing. Am J Physiol, 1999, 276: G387-392.
    8. Chen JD, Qian L, Ouyang H, et al. Gastric electrical stimulation with short pulses reduces vomiting but not dysrhythmias in dogs. Gastroenterology, 2003, 124: 401-409.
    9. de Csepel J, Goldfarb B, Shapsis A, et al.Electrical stimulation for gastroparesis. Gastric motility restored. Surg Endosc, 2006, 20: 302-306.
    10. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology, 2003,125: 421-428.
    11. Xing JH, Chen JD: Gastric electrical stimulation with parameters for gastroparesis enhances gastric accommodation and alleviates distention-induced symptoms in dogs. Dig Dis Sci, 2006,51: 2160-2164.
    12. Song G, Hou X, Yang B, et al. Efficacy and efficiency of gastric electrical stimulation with short pulses in the treatment of vasopressin-induced emetic responses in dogs. Neurogastroenterol Motil, 2006, 18: 385-391.
    13.王静,杨斌,李国华等.辣椒素阻断迷走神经后胃电起搏诱导大鼠脑c-fos表达研究.中华消化杂志,2005,25 (11):668-671.
    14.王静,杨斌,梁列新等.胃电刺激诱导大鼠延髓孤束核和迷走神经运动背核c-fos蛋白表达.胃肠病学,2006,11 (4):226-228.
    15. Liu J, Qiao X, Chen JD. Vagal afferent is involved in short-pulse gastric electrical stimulation in rats. Dig Dis Sci, 2004, 49 (5): 729-737.
    16. Liu J, Qiao X, Chen JD. Therapeutic potentials of a novel method of dual-pulse gastric electrical stimulation for gastric dysrhythmia and symptoms of nausea and vomiting. Am J Surg, 2006, 191 (2): 255-261.
    17. Rogers RC, Hermann GE, Travagli RA. Brainstem pathways responsible for oesophageal control of gastric motility and tone in the rat. J Physiol, 1999, 514 (Pt 2): 369-383.
    18. Mulak A, Kahane P, Hoffmann D, et al. Brain mapping of digestive sensations elicited by cortical electrical stimulations. Neurogastroenterol Motil, 2008, 20 (6): 588-596.
    19. Xu L, Sun X, Lu J, et al. Effects of gastric electric stimulation on gastric distention responsive neurons and expressions of CCK in rodent hippocampus. Obesity (Silver Spring), 2008, 16 (5): 951-957.
    20. Guan Y, Tang M, Jiang Z, et al. Excitatory effects of motilin in the hippocampus on gastric motility in rats. Brain Res, 2003, 984 (1-2): 33-41.
    21. Sudweeks SN, Hooft JA, Yakel JL. Serotonin 5-HT(3) receptors in rat CA1 hippocampal interneurons: functional and molecular characterization. J Physiol, 2002, 544 (Pt 3): 715-726.
    22. McDonald AJ, Mascagni F. Neuronal localization of 5-HT type 2A receptor immunoreactivity in the rat basolateral amygdale. Neuroscience, 2007, 146 (1): 306-320.
    23. De Jonghe BC, Horn CC. Chemotherapy agent cisplatin induces 48-h Fos expression in the brain of a vomiting species, the house musk shrew (Suncus murinus). Am J Physiol Regul Integr Comp Physiol, 2009 , 296 (4): R902-911.
    24. Mintchev MP, Sanmiguel CP, Amaris M, et al. Microprocessor-controlled movement of solid gastric content using sequential neural electrical stimulation. Gastroenterology, 2000 , 118 (2): 258-263.
    25. Bortolotto ZA, Collett VJ, Conquet F, et al. An analysis of the stimulus requirements for setting the molecular switch reveals a lower threshold for metaplasticity than synaptic plasticity. Neuropharmacology, 2008, 55 (4): 454-458.
    26. Schierloh A, Deussing J, Wurst W, et al. Corticotropin-releasing factor (CRF) receptor type 1-dependent modulation of synaptic plasticity. Neurosci Lett, 2007, 416 (1): 82-86.
    27. Lin Z, Forster J, Sarosiek I, et al. Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation. Diabetes Care, 2004, 27 (5): 1071-1076.
    28. Saab CY, Willis WD. Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex in the rat. Exp Brain Res, 2002, 146(1): 117-121.
    29. Lu CL, Wu YT, Yeh TC, et al. Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study. Neurogastroenterol Motil, 2004, 16 (5): 575-587.
    30. Terreberry RR, Neafsey EJ. Rat medial frontal cortex: a visceral motor region with a direct projection to the solitary nucleus. Brain Res, 1983, 278 (1-2): 245-249.
    31. Panteleev S, Grundy D. Descending influences from the infralimbic cortex on vago-vagal reflex control of gastric motor activity in the rat. Auton Neurosci, 2000, 86 (1-2): 78-83.
    1. Drossman DA. Presidential address: Gastrointestinal illness and the biopsychosocial model. Psychosom Med, 1998, 60 (3): 258-267.
    2.平丽,李瑜元,聂玉强,等.功能性胃肠病患病情况调查.实用医学杂志,2003,19(4):424-426.
    3.孙艳芳,李延青,王亚平.84例功能性消化不良合并肠易激综合征患者的临床症状调查.山东医药,2006,46(13):3.
    4. Shaib Y, El-Serag HB. The prevalence and risk factors of functional dyspepsia in a multiethnic population in the United States. Am J Gastroenterol, 2004, 99: 2210-2216.
    5. Halder SL, Locke GR 3rd, Schleck CD. Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study. Gastroenterology, 2007, 133 (3): 799-807.
    6. Chen M, Xiong L, Chen H, Xu A, He L, Hu P. Prevalence, risk factors and impact of gastroesophageal reflux disease symptoms: a population-based study in South China. Scand J Gast roenterol, 2005, 40: 759-767.
    7.许军英,谢小平,侯晓华.食管运动功能在重度反流性食管炎中的地位.中华内科杂志,2005,44(5):353-355.
    8.孙晓红,柯美云,王智凤,等.膈脚屏障及食管体部清除功能在胃食管反流中的作用.中国医学科学院学报,2002,24(03):289-293.
    9. Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol, 2003, 98 (4): 783-788.
    10.蓝宇,柯美云,王智凤,张利,陈艳敏.功能性消化不良患者体表胃电图类型及其临床意义.基础医学与临床,2003,23(03):322-326.
    11. Choi MG, Camilleri M, O'Brien MD, et al. A pilot study of motility and tone of the left colon in patients with diarrhea due to functional disorders and dysautonomia. Am J Gastroenterol, 1997, 92 (2): 297-302.
    12. Larsson MH, Simr(?)n M, Thomas EA, et al. Elevated motility-related transmucosal potential difference in the upper small intestine in the irritable bowel syndrome. Neurogastroenterol Motil, 2007, 19 (10): 812-820.
    13. Haag S, Talley NJ, Holtmann G. Symptom patterns in functional dyspepsia and irritable bowel syndrome: relationship to disturbances in gastric emptying and response to a nutrient challenge in consulters and non-consulters. Gut, 2004, 53 (10): 1445-1451.
    14. Pallotta N, Pezzotti P, Corazziari E. Relationship between antral distension and postprandial symptoms in functional dyspepsia. World J Gastroenterol, 2006, 12 (43): 6982-6991.
    15.杨敏,房殿春,李兆申,等.非糜烂型反流病患者食管内脏高敏感性与食管下括约肌局部降钙素基因相关肽阳性神经纤维的关系.胃肠病学,2006,11(1):16-20.
    16.侯晓华,李启祥,谢小平,等.功能性消化不良患者的胃液体排空和胃感觉阈异常.胃肠病学,2000,5(3):166-168.
    17.何旭东,徐章,侯晓华.不同水温下饮水负荷试验测定功能性消化不良患者胃感觉功能的研究.临床内科杂志,2007,24(6):415-416.
    18. Bratten J, Jones MP. Prolonged Recording of Duodenal Acid Exposure in Patients With Functional Dyspepsia and Controls Using a Radiotelemetry pH Monitoring System. J Clin Gastroenterol. 2009, Epub ahead of print.
    19. Lee KJ, Vos R, Janssens J, Tack J. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am J Physiol Gastrointest Liver Physiol, 2004, 286 (2): G278-284.
    20. Lee KJ, Kim JH, Cho SW. Dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification. J Gastroenterol Hepatol, 2006, 21 (3): 515-520.
    21. Pilichiewicz AN, Feltrin KL, Horowitz M, et al. Functional dyspepsia is associated with a greater symptomatic response to fat but not carbohydrate, increased fasting and postprandial CCK, and diminished PYY. Am J Gastroenterol, 2008, 103 (10): 2613-23.
    22. Fried M, Feinle C. The role of fat and cholecystokinin in functional dyspepsia. Gut, 2002, 51 Suppl 1: i54-57.
    23. Corsetti M, Cesana B, Bhoori S, et al. Rectal hyperreactivity to distention in patients with irritable bowel syndrome: role of distention rate. Clin Gastroenterol Hepatol, 2004, 2 (1): 49-56.
    24.王伟岸,潘国宗,钱家鸣,精神因素对肠易激综合征患者内脏敏感性的影响.中华医学杂志,2002,82(5):308-311.
    25.杨敏,房殿春,胡志安,等.内脏高敏感状态下食管酸灌注诱导的鼠脊髓背角c-Fos基因表达的研究.重庆医学,2007,36(15):1508-1510.
    26. Schicho R, Donnerer J, Liebmann I, et al. Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation. Brain Res, 2005, 1039 (1-2): 108-111.
    27. 27. di Mario F, Stefani N, B(?) ND, Natural course of functional dyspepsia after Helicobacter pylori eradication: a seven-year survey. Dig Dis Sci, 2005, 50 (12): 2286-2295.
    28. Sarnelli G, Cuomo R, Janssens J, Tack J. Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori. Dig Dis Sci, 2003, 48 (12): 2229-3226.
    29. Rhee PL, Kim YH, Son HJ et al. Lack of association of Helicobacter pylori infection with gastric hypersensitivity or delayed gastric emptying in functional dyspepsia. Am J Gastroenterol, 1999, 94 (11): 3165-3169.
    30. Turkkan E, Uslan I, Acarturk G, Does Helicobacter pylori-induced inflammation of gastric mucosa determine the severity of symptoms in functional dyspepsia? J Gastroenterol, 2009, 44 (1): 66-70.
    31. Andersen LP, Holck S, Janulaityte-G(u|¨)nther D. Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infection. FEMS Immunol Med Microbiol, 2005, 44 (2): 233-238.
    32. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology, 2002, 122 (7): 1738-1747.
    33. Ji S, Park H, Lee D, et al. Post-infectious irritable bowel syndrome in patients with Shigella infection. J Gastroenterol Hepatol, 2005, 20 (3): 381-386.
    34. Gwee KA, Collins SM, Read NW, et al. Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut, 2003, 52 (4): 523-526.
    35.魏良洲,鞠辉,戴素美,等.感染后肠易激综合征患者结肠粘膜P物质与白细胞介素、干扰素表达的相关性研究.中华消化杂志,2006,26 (9):586-589.
    36. Mulak A, Bonaz B. Irritable bowel syndrome: a model of the brain-gut interactions. Med Sci Monit, 2004, 10 (4): RA55-62.
    37. Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol, 2009, 6 (5): 306-314.
    38. Berthoud HR, Jedrzejewska A, Powley TL. Simultaneous labeling of vagal innervation of the gut and afferent projections from the visceral forebrain with dil injected into the dorsal vagal complex in the rat. J Comp Neurol, 1990, 301 (1): 65-79.
    39. Furness JB, Clerc N, Vogalis F, Stebbing MJ. 2003. The enteric nervous system and its extrinsic connections. In: Yamada T, Alpers DH, Kaplowitz N, Laine L, Owyang C, Powell DW, editors. Textbook of gastroenterology. Philadelphia: Lippincott Williams & Wilkins. pp 12-33.
    40.朱良如,谢小平,钱伟,等.5-羟色胺在胃机械感觉过敏中的作用.中华消化杂志,2005,25(3):166-168.
    41. M(o|¨)nnikes H, van der Voort IR, Wollenberg B, et al. Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia. Digestion, 2005, 71 (2): 111-123.
    42. Zhong F, Christianson JA, Davis BM, et al. Dichotomizing Axons in Spinal and Vagal Afferents of the Mouse Stomach. Dig Dis Sci, 2008, 53 (1): 194-203.
    43. Kechagias S, Botella S, Petersson F, et al. Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa. Scand J Gastroenterol, 2005, 40 (7): 775-782.
    44. Ward SM, Bayguinov J, Won KJ, et al. Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol, 2003, 465 (1): 121-135.
    45. Klaus Bielefeldt, Fang Zhong, H. Richard Koerber, et al. Phenotypic characterization of gastric sensory neurons in mice. Am J Physiol Gastrointest Liver Physiol, 2006, 291: G987-G997.
    46.杨小军,官阳,钱伟,等.突触可塑性在急性束缚应激所致内脏高敏感中的作用.中华消化杂志,2007,27(10):670-674.
    47. Yang M, Li ZS, Xu XR, et al. Characterization of cortical potentials evoked by oesophageal balloon distention and acid perfusion in patients with functional heartburn. Neurogastroenterol Motil, 2006, 18 (4): 292-299.
    48. Mulak A, Kahane P, Hoffmann D, et al. Brain mapping of digestive sensations elicited by cortical electrical stimulations. Neurogastroenterol Motil, 2008, 20 (6): 588-596.
    49. Terreberry RR, Neafsey EJ. Rat medial frontal cortex: a visceral motor region with a direct projection to the solitary nucleus. Brain Res, 1983, 278 (1-2): 245-249.
    50. Panteleev S, Grundy D. Descending influences from the infralimbic cortex on vago-vagal reflex control of gastric motor activity in the rat. Auton Neurosci, 2000, 86 (1-2): 78-83.
    51. Vandenbergh J, Dupont P, Fischler B, et al. Regional brain activation during proximal stomach distention in humans: A positron emission tomography study. Gastroenterology, 2005, 128 (3): 564-573.
    52. Ladabaum U, Minoshima S, Hasler WL, et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology, 2001, 120 (2): 369-376.
    53. Vandenberghe J, Dupont P, Van Oudenhove L, et al. Regional cerebral blood flow during gastric balloon distention in functional dyspepsia. Gastroenterology, 2007, 132 (5): 1684-1693.
    54. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology, 2000, 118 (5): 842-848.
    55. Xu L, Sun X, Lu J, et al. Effects of gastric electric stimulation on gastric distention responsive neurons and expressions of CCK in rodent hippocampus. Obesity (Silver Spring), 2008, 16 (5): 951-957.
    56. Guan Y, Tang M, Jiang Z, et al. Excitatory effects of motilin in the hippocampus on gastric motility in rats. Brain Res, 2003, 984 (1-2): 33-41.
    57. Sudweeks SN, Hooft JA, Yakel JL. Serotonin 5-HT(3) receptors in rat CA1 hippocampal intemeurofis: functional and molecular characterization. J Physiol, 2002, 544 (Pt 3): 715-726.
    58. McDonald AJ, Mascagni F. Neuronal localization of 5-HT type 2A receptor immunoreactivity in the rat basolateral amygdale. Neuroscience, 2007, 146 (1): 306-320.
    59. Saab CY, Willis WD. Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex in the rat. Exp Brain Res, 2002, 146 (1): 117-121.
    60.周吕,柯美云.神经胃肠病学与动力:基础与临床.北京:科学出版社.2005.712-728.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700