硫化氢对贲门失弛缓症动物模型食管重塑的治疗作用

Therapeutic Effect of Hydrogen Sulfide on Esophageal Remodeling in Animal Model of Achalasia

背景:贲门失弛缓症是一种病因尚不明确的食管动力障碍性疾病,表现为食管壁内神经丛不可逆性损伤导致下食管括约肌(LES)松弛功能障碍。研究发现贲门失弛缓症患者的食管下端平滑肌呈现重塑现象。目的:探讨硫化氢治疗对贲门失弛缓症动物模型食管重塑标志物表达的影响。方法:予BALB/c小鼠LES注射苄基二甲基十四烷基氯化铵(BAC)建立贲门失弛缓症动物模型,并予腹腔注射外源性硫化氢供体硫氢化钠。比较接受与未接受硫化氢治疗的模型小鼠以及对照组小鼠的食管测压结果,以免疫组化染色检测食管重塑标志物肌动蛋白、弹性蛋白表达。结果:成功建立贲门失弛缓症小鼠模型。与对照组相比,模型组和治疗组小鼠LES压力增高,肌动蛋白、弹性蛋白表达增强(P<0.05),治疗组上述指标的变化均轻于模型组(P<0.05)。结论:贲门失弛缓症动物模型食管下端存在重塑现象,硫化氢治疗可抑制食管重塑,为硫化氢用于治疗贲门失弛缓症提供了理论依据。

Background:Achalasia is an esophageal motility disorder with unclear etiology.It is characterized by impaired relaxation of the lower esophageal sphincter(LES)caused by irreversible damage to the myenteric plexus of esophagus.Remodeling of lower esophageal smooth muscle has been observed in patients with achalasia.Aims:To investigate the effect of hydrogen sulfide on expression of esophageal remodeling biomarker in animal model of achalasia.Methods:The animal model of achalasia was established by administering benzyldimethyltetradecylammonium chloride(BAC)into the LES in BALB/c mice.Fifteen model mice(treatment group)were administered with sodium hydrosulfide,an exogenous hydrogen sulfide donor,intraperitoneally.The results of esophageal manometry,as well as the expressions of two esophageal remodeling biomarker(actin and elastin,determined by immunohistochemistry)were compared between model mice with or without hydrogen sulfide treatment and the blank control mice.Results:The mouse model of achalasia was established successfully.Compared with the blank control group,the LES pressure and expressions of actin and elastin were significantly increased in model group and treatment group(P<0.05),and the increase was less in treatment group than in model group(P<0.05).Conclusions:Remodeling of lower esophagus is existed in animal model of achalasia.Hydrogen sulfide can inhibit the esophageal remodeling,which provides a theoretical basis for the treatment of achalasia with hydrogen sulfide.