贲门失弛缓症患者食管硫化氢合成酶表达的研究

Study on Expressions of Hydrogen Sulfide-producing Enzymes in Esophagus of Patients with Achalasia

背景:贲门失弛缓症是一种原发性食管动力障碍性疾病,目前普遍认为其发生与抑制性神经递质减少有关。硫化氢为胃肠道抑制性神经递质之一,胱硫醚-β-合酶(CBS)和胱硫醚-γ-裂解酶(CSE)是参与其合成的关键酶。目的:比较CBS和CSE在贲门失弛缓症患者与对照者食管组织中的表达差异,初步探讨硫化氢与贲门失弛缓症之间的关系。方法:纳入2013年1月—2015年6月在天津医科大学总医院行经口内镜肌切开术治疗的贲门失弛缓症患者25例,10例因食管鳞状细胞癌行食管切除术的患者作为对照组,分别取病变和正常下食管括约肌(LES)环肌组织,行CBS、CSE免疫组化染色,以半定量法评估两者的表达减少程度。结果:CBS、CSE免疫阳性物质主要分布于LES肌间神经丛。与对照组相比,贲门失弛缓症组LES组织中的CBS、CSE表达显著减少(P均<0.05),60.0%以上的患者几乎或完全无表达,而对照组多为强阳性表达。结论:贲门失弛缓症患者LES组织中硫化氢合成酶表达减少甚至缺失,提示硫化氢合成减少与贲门失弛缓症的发生、发展之间存在关联。

Background：Achaiasia is a primary esophageal motility disorder. It has been widely accepted that the occurrence of aehalasia is associated with reduction of inhibitory neurotransmitters. Hydrogen sulfide, which is known as a gastrointestinal inhibitory neurotransmitter, is produced endogenously from L-cysteine mainly via cystathionine beta-synthetase （CBS） and cystathionine gamma-lyase （CSE）. Aims ： To explore the relationship between hydrogen sulfide and aehalasia by comparing the expressions of CBS and CSE in esophagus of patients with aehalasia and the control subjects. Methods： Twenty-five achalasia patients undergoing peroral endoscopic myotomy from Jan. 2013 to Jun. 2015 at the Tianjin Medical University General Hospital were enrolled. Circular muscle samples in lower esophageal sphincter （LES） were obtained for detection of CBS and CSE immunohistochemically, and normal LES circular muscle samples from 10 patients with esophageal squamous carcinoma were served as controls. Reductions of CBS and CSE were evaluated semi-quantitatively. Results： Immunoreactivities for CBS and CSE were observed mainly in myenteric nerve plexus of LES. Compared with control subjects, expressions of CBS and CSE in LES of achalasia patients were significantly reduced （P all 〈 0.05）. More than 60% of the achalasia patients revealed severe reduction to complete loss of CBS and CSE immunoreactivities, whereas most of the control subjects were strongly positive for these two enzymes. Conclusions： Hydrogen sulfide-producing enzymes are significantly reduced and even absent in LES of patients with achalasia, which indicates that there exists a correlation between reduced hydrogen sulfide synthesis and achalasia.