Rodrigues David M, Lourenssen Sandra R, Kataria Jay, Paterson William G, Blennerhassett Michael G, Bechara Robert
Division of Gastroenterology, Queen's School of Medicine, Hotel Dieu Hospital, Kingston, ON, Canada.
Gastrointestinal Diseases Research Unit, Kingston General Hospital, Kingston, ON, Canada.
J Neurogastroenterol Motil. 2024 Apr 30;30(2):166-176. doi: 10.5056/jnm23024. Epub 2023 Aug 2.
BACKGROUND/AIMS: Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters.
Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score.
Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1.
The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.
背景/目的：贲门失弛缓症是一种以下食管括约肌松弛功能受损和食管无蠕动为特征的疾病，主要由抑制性神经支配丧失引起。然而，关于食管平滑肌的相关变化知之甚少。我们研究了环形平滑肌的收缩表型和神经支配，以及炎症状态，并将这些与患者特定参数相关联。
对连续接受经口内镜下肌切开术的贲门失弛缓症患者获取环形平滑肌活检组织。通过免疫细胞化学确定轴突神经支配和神经递质亚型，并将其与定量聚合酶链反应（qPCR）一起用于表征平滑肌增殖、细胞表型以及胶原蛋白表达。将这些结果与食管切除术时获取的对照组织进行比较，并与包括年龄、症状发作和埃克哈特评分在内的患者人口统计学因素相关联。
从25例贲门失弛缓症患者获取了平滑肌活检组织。总体而言，与对照组相比，肥大细胞数量增加、胶原蛋白沉积增加，但平滑肌细胞增殖增加。与对照组相比，轴突密度显著下降，贲门失弛缓症各亚型之间无差异。免疫细胞化学分析显示收缩标记物α-平滑肌肌动蛋白的表达增加，主要在1型贲门失弛缓症中，且随疾病持续时间增加，而qPCR鉴定出平滑肌蛋白的mRNA增加，肌球蛋白重链和胶原蛋白3a1减少，但胶原蛋白1a1未减少。
贲门失弛缓症中增厚的环形平滑肌层大多去神经支配，收缩表型和纤维化发生改变。经口内镜下肌切开术期间获取的活检组织为进一步研究贲门失弛缓症的病理生理学提供了一种手段。
