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Experimental studies on pathogenesis of duodenal ulcer ii. morphological alteration in brunner's glands in cysteamine induced duodenal ulcer in rats



Experimental studies on pathogenesis of duodenal ulcer ii. morphological alteration in brunner's glands in cysteamine induced duodenal ulcer in rats



Sapporo Medical Journal 57(2): 153-162



To clarify the pathogenesis of duodenal ulcer and the mucosal mechanism of the duodenum, which is continuously exposed to excessive H+ in the gastric juice, the morphological alterations in Brunner's glands were observed using cysteamine-induced duodenal ulcer in rats. The results were as follows; 1) Periodic acid Schiff (PAS)-positivity and glycoprotein M2 distribution in the Brunner's glands were markedly reduced after cysteamine administration. The dilatation and flatness of the Brunner's gland cells were also induced by cysteamine administration. These morphological alterations in the Brunner's glands were remarkably inhibited by pretreatment with secretin or cetraxate. 2) Electron microscopically, the apical cytoplasm of the Brunner's gland cells was filled with numerous secretory granules (SG) and the cells showed a characteristic convex appearance toward the lumen in the control group, whereas these SG remarkably decreased in number and subsequently the cells showed a concave appearance toward the lumen after cysteamine administration. Marked flatness of the Brunner's gland cells with microvilli was also demonstrated after cysteamine administration. However, no significant morphological alterations were found in the nucleus, rough-surfaced endoplasmic reticulum (RER), Golgi's apparatus, mitochondria and other organelles. 3) Pretreatment with either secretin, somatostatin, atropine or cetraxate, but not with cimetidine, clearly prevented the above electron microscopic changes in the Brunner's gland cells caused by cysteamine administration. Interestingly, the SG appeared to increase in the group pretreated with somatostatin. 4) These electron microscopic findings were supported by morphometric analysis using a computerized image analyzer. Namely, %SG (ratio of the area occupied by SG to Brunner's gland cells) slightly decreased 1 hour after and significantly decreased 12 hours after cysteamine administration compared with that in the untreated group. No significant changes in the %SG were found in the group pretreated with secretin, atropine, cimetidine 1 hour after cysteamine administration, whereas a significant increase in the %SG was found in the group pretreated with somatostatin or cetraxate. In addition, the reduction of the %SG seen 12 hours after cysteamine administration was significantly prevented by pretreatment with secretin, somatostatin, atropine or cetraxate, but was not inhibited by cimetidine. These results strongly suggested that the morphological changes in the duodenal Brunner's glands, which were confirmed by histological, immunohistological and electron microscopic observations, were associated with the pathogenesis and development of the duodenal ulcer and it was surmised that the Brunner's glands played an important role in the duodenal mucosal protection mechanism.

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Accession: 005426110

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