迷走神经C传入纤维通路在胃食管反流性咳嗽中的作用  

Role of C afferent fiber pathway of vagus nerve in gastroesophageal reflux cough

作　　者：平明芳 杨霞[1] 刘伟荣[5] 顾伟忠[3] 舒小莉[4] 江米足[1] PING Mingfang;YANG Xia;LIU Weirong;GU Weizhong;SHU Xiaoli;JIANG Mizu(Department of Gastroenterology and Pediatric Endoscopy Center,Children's Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China;不详)

机构地区：[1]浙江大学医学院附属儿童医院消化科和儿童内镜中心,310052 [2]嘉兴市第二医院儿科 [3]浙江大学医学院附属儿童医院病理科 [4]浙江大学医学院附属儿童医院消化实验室 [5]绍兴市人民医院儿科

出　　处：《浙江医学》2022年第14期1469-1473,1480,I0003,共7页Zhejiang Medical Journal

基　　金：国家自然科学基金面上项目(81270459)。

摘　　要：目的探讨迷走神经C传入纤维通路在胃食管反流性咳嗽中的作用。方法普通级健康雄性Wistar新生大鼠45只,按随机数字表法分为4组:R1组、R2组、R4组大鼠各10只,R3组大鼠15只。R1组:阳性对照组(盐酸灌注组);R2组:暂时性食管迷走神经C传入纤维变性型实验组;R3组:持久性食管迷走神经C传入纤维变性型实验组;R4组:阴性对照组(0.9%氯化钠溶液灌注组)。所有小鼠均喂养至8周,麻醉后按照以下方式完成建模:R1组用浓度0.1 mol/L盐酸溶液连续灌注2周;R2组皮下连续注射50 mg/kg辣椒素2 d后,给予酸灌注2周;R3组在出生2 d后,先皮下注射50 mg/kg辣椒素,连续2 d,8周龄后连续酸灌注2周;R4组连续食管内0.9%氯化钠溶液灌注2周。采用支气管激发试验检测大鼠吸入不同浓度的乙酰甲胆碱(Mch)后大鼠的肺顺应性及肺阻力的变化;HE染色观察4组大鼠气管组织、肺组织和食管组织的病理改变;RT-PCR法检测肺组织中神经激肽受体1(NK_(1)R)、神经激肽受体2(NK_(2)R)、神经激肽受体3(NK_(3)R)mRNA表达水平及食管组织中5-羟色胺受体3(5-HT_(3)R)、瞬时感受器电位香草酸受体1(TRPV1)和酸敏感离子通道3(ASIC3)mRNA表达水平。结果当Mch浓度升到0.25、0.5 mmol/L时,R1组大鼠肺阻力增加百分比明显大于R2组、R3组、R4组(均P<0.05);当Mch浓度升到0.5 mmol/L时,R1组大鼠动态肺顺应性减少百分比大于R2组、R3组及R4组(均P<0.05)。HE染色发现,与R1组比较,R2、R3和R4组大鼠气管组织纤毛柱状上皮无明显增厚,炎症细胞浸润不明显;肺组织仅见少量炎症细胞浸润;食管组织鳞状上皮增厚不明显,固有层炎症细胞浸润较少等。各组大鼠肺组织中NK_(1)R、NK_(2)R mRNA表达水平比较差异均无统计学意义(均P>0.05),R3组大鼠肺组织中NK_(3)R mRNA表达水平高于R1组、R2组和R4组,差异均有统计学意义(均P<0.05)。各组大鼠食管组织中5-HT_(3)R、TRPV1和ASIC3 mRNA表达水平比较差�Objective To determine the effect of C afferent fiber pathawy of vagus nerve in gastroesophageal reflux cough.Methods Forty-five male newborn Wistar rats were randomly divided into 4 groups:R1(n=10),R2(n=10),R3(n=15)and R4(n=10)groups.All rats were fed for 8 weeks,rats in R1 group were continuously perfused with 0.1 mol/L hydrochloric acid solution for 2 weeks to induce gastroesophageal reflux cough model;after continuous subcutaneous injection of 50 mg/kg capsaicin for 2 d,rats in R2 group were given acid perfusion for 2 weeks;rats in R3 group was given subcutaneous injection of 50 mg/kg capsaicin for 2 days after birth,and then fed to 8 weeks of age,followed by continuous acid perfusion for 2 weeks;rats in R4 group were continuously perfused with 0.9% sodium chloride solution in the esophagus for 2 weeks(negative control group).Bronchial challenge test was used to detect the changes of pulmonary compliance and pulmonary resistance in rats after inhaling different concentrations of methacholine(Mch);the pathological changes of trachea,lung tissues and esophagus were observed.The mRNA expression of 5HT_(3)R,TRPV1 and ASIC3 of bronchial and lung tissues and NK_(1)R,NK_(2)R,NK_(3)R of esophageal tissue were measured by RT-PCR.Results Compared with the percentage increase in pulmonary resistance of rats in R1 group,when the concentration of Mch increased to 0.25 and 0.5 mmol/L,R2,R3,and R4 groups had higher pulmonary resistance;the lung resistance in rats was significantly decreased(all P<0.05).However,when the concentration of Mch increased to 0.5 mmol/L,the reduction percentage of dynamic lung compliance in R2,R3 and R4 groups were significantly lower than that in R1 group(all P<0.05).Compared with R1 group,the ciliated columnar epithelium of the trachea in R2,R3 and R4 groups had no significant thickening,and the inflammatory cell infiltration was not significant;only a small amount of inflammatory cell infiltration was seen in the lung tissue;while the thickening of the squamous epithelium of the esophagus and l

关 键 词：迷走神经C传入纤维 胃食管反流性咳嗽 瞬时感受器电位香草酸受体1 酸敏感离子通道3 气道高反应性 

分 类 号：R571[医药卫生—消化系统]