Alterations of the enteric smooth musculature in diverticular disease
Alterations of the enteric smooth musculature in diverticular disease
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DOI：
10.1007/s00535-013-0886-y
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发表时间：
2014-08-01
影响因子：
6.3
通讯作者：
Wedel, Thilo
中科院分区：
文献类型：
--
作者：
Hellwig, Ines;Boettner, Martina;Wedel, Thilo
憩室病(DD)的发病机制被认为是多因素的，涉及肠道运动障碍和潜在的肠道神经肌肉病理。虽然肠道神经病变已经有了很好的文献记载，但关于伴随的肠道肌肉系统变化的实际研究却很有限。本研究旨在通过组织学、超微结构和分子生物学方法重新评估平滑肌组织。全层乙状结肠标本来自20例DD患者和19例正常对照。用形态计量学方法评价环肌层、纵肌层和肌间神经丛的厚度和结缔组织指数。用光学显微镜和透射电子显微镜观察其结构变化。用定量聚合酶链式反应(QPCR)检测收缩肌器各成分(包括平滑肌α-肌动蛋白、滑膜蛋白、组蛋白脱乙酰酶8和平滑肌肌球蛋白重链)的基因表达谱。免疫组织化学结果显示，与对照组相比，DD患者表现为(1)环状肌层和纵肌层厚度增加，(2)平滑肌细胞结构改变，(3)纵肌层结缔组织指数增加，(4)超微结构水平局部肌丝密度降低，(5)SMMHC基因表达水平特异性下调，(6)SMMHC免疫反应性降低，(7)少神经元神经节细胞减少。肠源性肌病以肌肉构筑紊乱、结缔组织替代和特定肌丝丢失为特征，可能与DD的发生和发展有关。
The pathogenesis of diverticular disease (DD) is considered to be multifactorial and involves intestinal motor disturbances and an underlying enteric neuromuscular pathology. While an enteric neuropathy has been well documented, actual studies on concomitant alterations of the enteric musculature are limited. This study is aimed at reassessing the smooth muscle tissue by histological, ultrastructural and molecular-biological approaches.Full-thickness sigmoid specimens were obtained from patients with DD (n = 20) and controls (n = 19). Morphometric analysis was performed to evaluate the thickness and connective tissue index of the circular and longitudinal muscle layers as well as the myenteric plexus. Structural alterations were determined by light and transmission electron microscopy. mRNA profiles of components of the contractile smooth muscle apparatus including smooth muscle alpha-actin, smoothelin, histone deacetylase 8, and smooth muscle myosin heavy chain (SMMHC) were assessed by qPCR. Altered gene expression levels were confirmed at protein level by immunohistochemistry.Compared to controls, patients with DD showed (1) increased thickness of the circular and longitudinal muscle layers, (2) architectural alterations of smooth muscle cells, (3) increased connective tissue index of the longitudinal muscle layer, (4) focally reduced density of myofilaments at ultrastructural level, (5) specific down-regulation of SMMHC mRNA levels, (6) decreased immunoreactivity of SMMHC, (7) oligo-neuronal hypoganglionosis.DD is associated with distinct structural and functional alterations of the enteric musculature. The enteric myopathy is characterized by disturbed muscular architecture, connective tissue replacement and loss of specific myofilaments and thus may contribute to the pathogenesis and progression of DD.