AXONAL NECROSIS OF ENTERIC AUTONOMIC NERVES IN CONTINENT ILEAL POUCHES - POSSIBLE IMPLICATIONS FOR PATHOGENESIS OF CROHNS-DISEASE
AXONAL NECROSIS OF ENTERIC AUTONOMIC NERVES IN CONTINENT ILEAL POUCHES - POSSIBLE IMPLICATIONS FOR PATHOGENESIS OF CROHNS-DISEASE
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DOI：
10.1097/00000658-199303000-00008
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发表时间：
1993-03-01
影响因子：
9
通讯作者：
SILEN, W
中科院分区：
文献类型：
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作者：
DVORAK, AM;ONDERDONK, AB;SILEN, W
目的首次在克罗恩病患者的小肠标本中发现轴索坏死(A.M.Dvorak等人)。《Hum Pathol》1980；11：620-634)。临床上明显的可控性回肠(袋)炎症具有类似克罗恩病的临床特征。利用超微结构和微生物学手段鉴定受损的肠神经和组织细菌，寻找克罗恩病和膀胱炎发病机制上可能的相似性。方法对114例人类肠道标本的重复活检进行编码的超微结构和微生物学研究。取自溃疡性结肠炎、克罗恩病或家族性息肉病患者的回肠、结肠、传统回肠造口术或可控膀胱术的活检标本，根据临床和内窥镜检查标准分为三组(对照组、正常膀胱组、膀胱炎组)。用标准方法为电子显微镜准备活检标本；复制的活检样本在准备培养物之前被广泛清洗，以鉴定需氧细菌以及兼性和专性厌氧细菌(Onderdonk等人)。临床微生物学杂志1992；30：312-317)。肠神经受损的超微结构诊断是基于先前发表的轴索坏死标准(A.M.Dvorak和W.Silen)。Ann Surg 1985；201：53-63)。组间比较采用卡方分析。结果无论是否存在细菌，克罗恩病对照活检组织中轴索坏死率最高(53%)。在细菌培养阳性的溃疡性结肠炎和家族性息肉病活检组织(无论活检部位)中，轴突坏死的发生率也高于无细菌培养阳性的患者(P<；0.001)。此外，42%的溃疡性结肠炎和家族性息肉病患者的眼袋活检组织中有轴突坏死，特别是在那些临床标准被发现发炎且活检组织细菌培养阳性的眼袋组织中。在培养阳性的情况下，来自溃疡性结肠炎和家族性息肉病患者的对照活检的神经损伤显著低于囊活检(p<；0.01)。在溃疡性结肠炎或家族性息肉病患者的临床炎症性肠袋活检中，我们发现当细菌培养为阴性时，没有人损伤肠神经(p<；0.005)。在溃疡性结肠炎患者的所有活检组织中，仅存在轴突坏死与未损伤的肠神经相比，溃疡性结肠炎活检合并轴突坏死的比例非常显著(P<；0.001)。结论克罗恩病轴索坏死的超微结构发现证实了先前的研究。阴囊炎患者肠神经受损的存在为阴囊炎和克罗恩病相似的临床印象提供了超微结构支持。阴囊炎中受损的神经和侵袭性细菌之间的联系表明克罗恩病的发病机制有相似之处，需要进一步研究。
Objective Axonal necrosis was first described in samples of small intestine from patients with Crohn's disease (A.M. Dvorak et al. Hum Pathol 1980; 11:620-634). Clinically evident inflammation of continent ileal reservoirs (pouches) has clinical features that resemble Crohn's disease. Possible similarities in the pathogenesis of Crohn's disease and pouchitis were sought using ultrastructural and microbiologic tools to identify damaged enteric nerves and tissue bacteria.Methods An encoded ultrastructural and microbiologic study of replicate biopsies from 114 samples of human intestine was done. Biopsies from ileum, colon, conventional ileostomy or continent pouch were obtained from patients with ulcerative colitis, Crohn's disease, or familial polyposis and grouped into three clinical study groups (control, normal pouch, pouchitis), based on clinical and endoscopic criteria. Biopsies were prepared for electron microscopy with standard methods; replicate biopsy samples were washed extensively before preparing cultures designed to identify aerobic as well as facultative and obligate anaerobic bacteria (Onderdonk et al. J Clin Microbiol 1992; 30:312-317). The ultrastructural diagnosis of damaged enteric nerves was based on previously published criteria for axonal necrosis (A.M. Dvorak and W. Silen. Ann Surg 1985; 201:53-63). Intergroup comparisons were tested for significance using Chi-square analysis.Results The highest incidence of axonal necrosis was present in Crohn's disease control biopsies (53%), regardless of whether bacteria were present (or not) in cultures of replicate biopsies. Axonal necrosis also occurred in more ulcerative colitis and familial polyposis biopsies (regardless of biopsy site) that had positive bacterial cultures than in those that did not (p < 0.001). In addition, axonal necrosis was documented in 42% of the pouch biopsies from ulcerative colitis and familial polyposis patients, particularly in those pouches that were found to be inflamed by clinical criteria and that also had positive bacterial cultures of the biopsied tissues. Control biopsies from patients with ulcerative colitis and familial polyposis had significantly less nerve damage than pouch biopsies in the presence of positive cultures (p < 0.01). Among the clinically inflamed pouches biopsied in ulcerative colitis or familial polyposis patients, we found that none had damaged enteric nerves when bacterial cultures were negative (p < 0.005). It the presence of axonal necrosis alone was compared with the presence of undamaged enteric nerves in all biopsies from patients with ulcerative colitis, a highly significant number of ulcerative colitis biopsies with axonal necrosis occurred in pouches (72%) compared with controls (p < 0.001).Conclusions The ultrastructural finding of axonal necrosis in Crohn's disease confirms previous studies. The presence of damaged enteric nerves in patients with pouchitis provides ultrastructural support to the clinical impression of similarities between pouchitis and Crohn's disease. The association of damaged nerves and invasive bacteria in pouchitis suggests mechanistic similarities for the pathogenesis of Crohn's disease that requires further investigation.