一过性食管下括约肌松弛动物模型的建立及其机制探讨
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摘要
目的建立一过性食管下括约肌松弛(TLESR)的大鼠模型并探讨其发生机制。方法 SD雄性大鼠随机分为4组:空白对照组、模型组、药物(saclofen)注射组、空白注射组,每组12只。通过逐次向胃内注水的方法建立胃扩张诱发TLESR的动物模型。药物注射组和空白注射组在进行胃扩张30 min前,用微量注射法往孤束核区注射GABAB受体阻断剂saclofen或改良Riger液。采用消化道动力检测系统检测、分析TLESR频率,采用免疫组织化学法观察孤束核区GABAB受体表达。结果模型组大鼠TLESR频率提高,GABAB受体表达减少,向孤束核区微量注射GABAB受体阻断剂可大幅提高TLESR频率。结论提示胃扩张造模成功,TLESR的发生与孤束核中GABAB受体调节密切相关。
Objective To establish a rat model of transient lower esophageal sphincter relaxation(TLESR) and explore its mechanism. Methods SD male rats were randomly divided into 4 groups: Blank control group, model group, drug(saclofen)injection group and blank injection group, with 12 rats in each group. An animal model of gastric expansion induced TLESR was established by successively injecting water into the stomach. The drug injection group and the blank injection group were injected with the GABAB receptor blocker saclofen or modified Riger solution into the solitary nucleus region by microinjection before the gastric dilation was performed for 30 min. The frequency of TLESR was detected and analyzed by digestive tract dynamic detection system, and the expression of GABAB receptor in the solitary nucleus was observed by immunohistochemistry. Results In the model group, the frequency of TLESR increased and the expression of GABAB receptor decreased. Microinjection of GABAB receptor blocker into the solitary tract nucleus region could significantly increase the frequency of TLESR. Conclusion It is suggested that the gastric dilatation model is successful, and the occurrence of TLESR is closely related to the regulation of GABAB receptor in the solitary tract nucleus.
Objective To establish a rat model of transient lower esophageal sphincter relaxation(TLESR) and explore its mechanism. Methods SD male rats were randomly divided into 4 groups: Blank control group, model group, drug(saclofen)injection group and blank injection group, with 12 rats in each group. An animal model of gastric expansion induced TLESR was established by successively injecting water into the stomach. The drug injection group and the blank injection group were injected with the GABAB receptor blocker saclofen or modified Riger solution into the solitary nucleus region by microinjection before the gastric dilation was performed for 30 min. The frequency of TLESR was detected and analyzed by digestive tract dynamic detection system, and the expression of GABAB receptor in the solitary nucleus was observed by immunohistochemistry. Results In the model group, the frequency of TLESR increased and the expression of GABAB receptor decreased. Microinjection of GABAB receptor blocker into the solitary tract nucleus region could significantly increase the frequency of TLESR. Conclusion It is suggested that the gastric dilatation model is successful, and the occurrence of TLESR is closely related to the regulation of GABAB receptor in the solitary tract nucleus.
引文
[1]中华医学会消化病学分会胃肠动力学组.胃食管反流病治疗共识意见(2007,西安)[J].中华消化杂志,2007,27(10):689-690.
[2]Dent J,Holloway RH,Toouli J,et al.Mechanisms of low esophageal sphincter incompetencein patients with symptomatic gastroesophageal reflux[J].Gut,1988,29(12):1020-1028.
[3]林三仁,许国铭,胡品津,等.中国胃食管反流病共识意见[J].胃肠病学,2007,12(4):233-239.
[4]查慧,谢小平,侯晓华.胃食管反流病患者酸反流与食管运动功能障碍的关系[J].胃肠病学,2006,11(1):41-44.
[5]于霞,阿依古力·阿不力米提,蒋丽丽.高分辨率食管测压及24 h食管阻抗-p H值对功能性烧心和非糜烂性反流病患者的监测结果分析[J].中国医学装备,2017,14(9):92-95.
[6]Kuo P,Bravi I,Marreddy U,et al.Postprandial cardiac vagal tone and transient lower esophageal sphincter relaxation(TLESR)[J].Neurogastroenterology&Motility the Official Journal of the European Gastrointestinal Motility Society,2013,25(10):841-e639.
[7]Fawley JA,Peters JH,Andresen MC.GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract[J].Journal of Neurophysiology,2011,106(4):1833.
[8]Boeckxstaens GE,Beaumont H,Mertens V.Effects of lesogaberan,a novel GABA(B)-receptor agonist,on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease[J].Gastroenterology,2010,139:377-379.
[9]Chi Wang,De-Feng Zhou,xiao-Wei Shuai,et al.Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats[J].World Journal of Gastroenterology(English Edition),2007,13(36):4873-4880.
[10]彭艳,易受乡,李振海,等.毫针不同刺激强度对胃扩张疼痛大鼠脊髓背角NMDA受体和P物质的影响[J].世界华人消化杂志,2009,17(13):1339-1345.
[11]Mittal RK,Holloway RH,Penagini R,et al.Transient lower esophageal sphincter relaxation[J].Gastroenterology,1995,109:601-610.
[12]王驰,陈欣,谢鹏雁,等.他克林对食管运动的影响及电针刺治疗[C].//2014中华医学会北京分会消化系病学术年会论文集,2014:77.
[13]Pin JP,Kniazeff J,Binet V,et al.Activation mechanism of the heterodimeric GABA(B)receptor[J].Biochemical Pharmacology,2004,68(8):1565-1572.
[14]Fawley JA,Peters JH,Andresen MC.GABA(B)-Mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract[J].Journal of Neurophysiology,2011,106(4):1833.
[15]Boeckxstaens GE,Beaumont H,Mertens V.Effects of lesogaberan,a novel GABA(B)-receptor agonist,on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease[J].Gastroenterology,2010,139:377-379.
[16]Boeckxstaens GE,Denison H,Jensen JM,et al.Translational gastrointestinal pharmacology in the 21st century:The lesogaberan story'[J].Current Opinion in Pharmacology,2011,11(6):630.
[17]Cossentino MJ,Mann K,Armbruster SP,et al.Randomised clinical trial:The effect of baclofen in patients with gastro-oesophageal reflux-a randomised prospective study[J].Alimentary Pharmacology&Therapeutics,2012,35(9):1036-1044.
[18]Tsoukali E,Sifrim D.The role of weakly acidic reflux in proton pump inhibitor failure,has dust settled[J].Journal of Neurogastroenterology&Motility,2010,16(3):258-264.
[19]陈姝,雍春燕,陈恒,等.胃扩张模型大鼠迷走神经脊核胃相关神经元对不同针刺穴位的反应[J].中国组织工程研究,2014,(36):5842-5846.
[2]Dent J,Holloway RH,Toouli J,et al.Mechanisms of low esophageal sphincter incompetencein patients with symptomatic gastroesophageal reflux[J].Gut,1988,29(12):1020-1028.
[3]林三仁,许国铭,胡品津,等.中国胃食管反流病共识意见[J].胃肠病学,2007,12(4):233-239.
[4]查慧,谢小平,侯晓华.胃食管反流病患者酸反流与食管运动功能障碍的关系[J].胃肠病学,2006,11(1):41-44.
[5]于霞,阿依古力·阿不力米提,蒋丽丽.高分辨率食管测压及24 h食管阻抗-p H值对功能性烧心和非糜烂性反流病患者的监测结果分析[J].中国医学装备,2017,14(9):92-95.
[6]Kuo P,Bravi I,Marreddy U,et al.Postprandial cardiac vagal tone and transient lower esophageal sphincter relaxation(TLESR)[J].Neurogastroenterology&Motility the Official Journal of the European Gastrointestinal Motility Society,2013,25(10):841-e639.
[7]Fawley JA,Peters JH,Andresen MC.GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract[J].Journal of Neurophysiology,2011,106(4):1833.
[8]Boeckxstaens GE,Beaumont H,Mertens V.Effects of lesogaberan,a novel GABA(B)-receptor agonist,on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease[J].Gastroenterology,2010,139:377-379.
[9]Chi Wang,De-Feng Zhou,xiao-Wei Shuai,et al.Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats[J].World Journal of Gastroenterology(English Edition),2007,13(36):4873-4880.
[10]彭艳,易受乡,李振海,等.毫针不同刺激强度对胃扩张疼痛大鼠脊髓背角NMDA受体和P物质的影响[J].世界华人消化杂志,2009,17(13):1339-1345.
[11]Mittal RK,Holloway RH,Penagini R,et al.Transient lower esophageal sphincter relaxation[J].Gastroenterology,1995,109:601-610.
[12]王驰,陈欣,谢鹏雁,等.他克林对食管运动的影响及电针刺治疗[C].//2014中华医学会北京分会消化系病学术年会论文集,2014:77.
[13]Pin JP,Kniazeff J,Binet V,et al.Activation mechanism of the heterodimeric GABA(B)receptor[J].Biochemical Pharmacology,2004,68(8):1565-1572.
[14]Fawley JA,Peters JH,Andresen MC.GABA(B)-Mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract[J].Journal of Neurophysiology,2011,106(4):1833.
[15]Boeckxstaens GE,Beaumont H,Mertens V.Effects of lesogaberan,a novel GABA(B)-receptor agonist,on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease[J].Gastroenterology,2010,139:377-379.
[16]Boeckxstaens GE,Denison H,Jensen JM,et al.Translational gastrointestinal pharmacology in the 21st century:The lesogaberan story'[J].Current Opinion in Pharmacology,2011,11(6):630.
[17]Cossentino MJ,Mann K,Armbruster SP,et al.Randomised clinical trial:The effect of baclofen in patients with gastro-oesophageal reflux-a randomised prospective study[J].Alimentary Pharmacology&Therapeutics,2012,35(9):1036-1044.
[18]Tsoukali E,Sifrim D.The role of weakly acidic reflux in proton pump inhibitor failure,has dust settled[J].Journal of Neurogastroenterology&Motility,2010,16(3):258-264.
[19]陈姝,雍春燕,陈恒,等.胃扩张模型大鼠迷走神经脊核胃相关神经元对不同针刺穴位的反应[J].中国组织工程研究,2014,(36):5842-5846.