失弛缓症患者血清可改变正常人胃底肠肌间神经丛化学信号和NO介导的反应  

Serum from achalasia patients alters neurochemical coding in the myenteric plexus and nitric oxide mediated motor response in normal human fundus

作　　者：Bruley Des Varannes S. Chevalier J. Pimont S. M. Neunlist 程妍(译) 陈云茹(校) 

机构地区：[1]不详 [2]INSERM U539, University Hospital HStel Dieu, Place Alexis Ricordeau, 44035 Nantes Cedex, France

出　　处：《世界核心医学期刊文摘（胃肠病学分册）》2006年第8期34-35,共2页Core Journals in Gastroenterology

摘　　要：Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (- 26% of NSE positive neurones; p = 0.016) and VIP (- 54% ; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+ 16% ; p< 0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (- 7.6 (2.6) v - 14.5 (5.0); p = 0.036). Conclusions: Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.Background and aims： Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods： man fundus were maintained in Specimens of normal huculture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease （GORD）, or healthy subjects （controls）. Immunohistochemical detection of choline acetyltransferase （CHAT）, neurone specific enolase （NSE）, vasoactive intestinal polypeptide （VIP）, nitric oxide synthase （NOS）, and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation （EFS） induced contractions were measured in circular muscle preparations. Results： Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS （ - 26% of NSE positive neurones; p = 0.016） and VIP （-54%; p = 0.09） neurones, and a concomitant increase in ChAT neurones （＋ 16%; p 〈 0. 001） compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations （abolished by N-nitro-L-arginine methyl ester） was significantly decreased following incubation with serum from achalasia patients compared with controls （ - 7.6 （2.6） v - 14.5 （5.0）, p = 0. 036）.

关 键 词：肠血管活性多肽 肌间神经丛 失弛缓症 收缩反应 正常人 患者 血清 NO介导 化学信号 胃底 

分 类 号：R392.3[医药卫生—免疫学] R322.85[医药卫生—基础医学]