痛泻要方对IBS-D内脏敏感性模型大鼠GABAA受体和NMDA受体的中枢敏化的作用于丰彦1黄绍刚3张海燕3王颖1童金生1黄怡1翁一洁1叶华4郑学宝2(1.广东医学院第二临床学院广东东莞524023)(2.广东医学院屮医研宄室广东东莞524023)(3.广东省屮医院大学城分院广东广州511495)(4.广东医学院广东天然药物研允与开发重点实验室广东湛江524023)【摘要】目的:探讨痛泻要方干预下IBS-D内脏敏感性模型人鼠GABAA受体和NMDA受体的屮枢敏化的作用。方法:建立内脏敏感性IBS-D火鼠动物模型,并予以痛泻要方干预,观察其腹部撤回反射(AWR)评分和小肠推进率,通过PT-PCR法检测其NMDA受体和GABAA受体在其脊髓屮的表达。结果:痛泻要方能显著降低NR1基因转录,提高GABAA受体基因转录。痛泻要方干预后压力提高明显,并同时能明显抑制正常大鼠的肠运动降低内脏敏感性IBS大鼠小肠推进速率。结论:痛泻要方可能对脊髓NMDA和GABA受体广泛的交互作用在内脏敏感性IBS大鼠屮枢敏感化屮发挥作用。【关键词】闪脏敏感性;IBS-D;痛泻要方;NMDA受体;GABA受体【中图分类号】R365【文献标识码】B【文章编号】1003-5028(2015)8-0660-03TongxieyaofanginIBS-DmodelofvisceralsensitivityinratsGABAAreceptorsandtheroleofcentralsensitizationofNMDAreceptorFengYanYul,HuangShaogang3,zhanghaiyan3,TongJinShengl,HuangYil,WengYiJiel,YeHua4,ZhengXuebao2(l.Thesecondclinicalcollegeofguangdongmedicalcollege,Dongguancity,Guangdongprovince,524023)(2.GuangdongmedicalcollegeoftraditionalChinesemedicineresearchDongguancity,Guangdongprovince,524023)(3.GuangdonghospitalofuniversitycitybranchGuangzhoucity,Guangdongprovince,511495)(4.GuangdongnaturalmedicineresearchanddevelopmentkeylaboratoryofguangdongmedicalcollegeZhanjiang,guangdongprovince,524023)【Abstract】Objective:TothisprojectintendstostudyTongxieyaofangintervenedD-IBSvisceralsensitivitymodelratsGABAAreceptorsandtheroleofcentralsensitizationofNMDAreceptor.Methods:EstablishIBSvisceralsensitivity-Danimalmodelinrats,andTongxieyaofangintervention,observeitsabdominalwithdrawalreflex(whorunsAWR)scoreandsmallintestinalpropulsionratesvisceralsensitivity,suchasthroughthePT-PCRmethodtodetecttheexpressionofNMDAreceptorsandGABAAreceptorsinthespinalcord.Results:TheexperimentattheeighthweekofseverediarrheacansignificantlyreducetheNR1genetranscription,increaseGABAAreceptorgenetranscription.Modelgroupandsinterventiongroupcarriedonabdominalpainandarchbackpressurecomparedwithnormalcontrolgroup,withsignificantdifference(P<0.05).Tongxieyaofangpressureincreasesignificantlyafterintervention,andatthesametimecanobviouslyinhibitnormalratintestinalmovementreducingvisceralsensitivityIBSratsmallintestinepropulsionrate.Conclusion:TongxieyaofangeffectsspinalNMDAandGABAreceptorcanbeawiderangeofinteractionsinthevisceralsensitivityIBSratcentralsensitization.【Keywords】visceralpainsensitivity,IBS,Tongxieyaofang,NMDAreceptor,GABAreceptors肠易激综合征(Irritablebowelsyndrome,IBS)是临床最常见的胃肠功能性疾病,腹泻型肠易激综合征(IBS-D)是IBS的一个主要临床亚型,约占所有IBS的60%左右,具有高发病率、反复难愈的特点[1]。IBS患者就诊的主要原因之一是腹部疼痛或腹部不适,内脏敏感性增高(VHL)始终是IBS的实验动物模型和临床患者必备的特征表现。己知脊髓背角作为脑一肠轴的“中继站”,是内脏敏感性调节和中枢敏化的关键部位[2]。近年来对IBS发病机制的研究显示,脊髓中枢对内脏感觉传入投射区域的敏感性升高是形成IBS内脏敏感性的重要机制[3-4]。N一甲基-D-门冬氨酸(N-methyl-D-asnartate,NMDA)受体和r-氨基丁酸型(r-Aminobutyricacid,GABA)A型受体分别是中枢神经系统中重要的兴奋性和抑制性受体,对外周伤害性信息的传递和表达的调控...