Paneth Cell Hyperplasia and Metaplasia in Hirschsprung-associated Enterocolitis in An Aganglionosis Rat Model

The Indonesian Biomedical Journal Pub Date : 2022-12-01 DOI:10.18585/inabj.v14i4.2007

I. R. Budianto, A. Firmansyah, Y. Moenadjat, A. A. Jusuf, V. Soetikno

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引用次数: 2

Abstract

BACKGROUND: Many hypotheses regarding the pathophysiology of enterocolitis in aganglionic megacolon or Hirschsprung disease (HSCR) has been proposed. Paneth cells are columnar intestinal epithelial cells that have an important role in maintaining of intestinal homeostasis as a bactericide. Since enterocolitis in HSCR may have association with Paneth cells metaplasia and hyperplasia, current study investigated Paneth cells metaplasia and hyperplasia in the sigmoid colon of HSCR rat model and its products, namely a-defensins and IL-1b, in the sigmoid colon tissues.METHODS: Aganglionosis-induced and control Sprague-Dawley rats were euthanized on Day (D)-7, -14, -17, -19, -21, -23, -25, and -28. Sigmoid colon tissue was isolated at each time point, and degree of enterocolitis as well as Paneth cells metaplasia and hyperplasia were analyzed by Hematoxylin-eosin staining, then protein levels of a-defensins and interleukin (IL)-1b were determined by enzyme-linked immunosorbent assay (ELISA).RESULTS: Enterocolitis scores increased with time. The Paneth cells metaplasia and hyperplasia were observed on D14 until D28 (p<0.01 vs. control group) followed by an increased in the levels of IL-1b. The levels of a-defensins protein expression were initially increased (D7-D14; p<0.01 vs. control group) but then undergo reciprocal changes on D19 until D28 (p<0.01 vs. D7 and D14). Positive correlations between the degree of enterocolitis and Paneth cells number were detected in the sigmoid colon (r=0.42).CONCLUSION: Paneth cells underwent metaplasia and hyperplasia in the sigmoid colon of HSCR rats corresponding to an increase in the degree of enterocolitis, but not followed by an increase in the level of a-defensins as well as IL-1b, suggesting that there is an involvement of Paneth cells in the pathophysiology of enterocolitis due to HSCR.KEYWORDS: Hirschsprung, enterocolitis, defensins; metaplasia, Paneth cell, animal model

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腺瘤病大鼠巨结肠相关性小肠结肠炎的Paneth细胞增生和化生

背景:关于神经节性巨结肠或巨结肠病(HSCR)的小肠结肠炎的病理生理学已经提出了许多假设。Paneth细胞是一种柱状肠上皮细胞，作为一种杀菌剂在维持肠道稳态中起着重要作用。由于HSCR小肠结肠炎可能与Paneth细胞化生和增生有关，本研究对HSCR大鼠模型乙状结肠Paneth细胞化生和增生及其产物乙状结肠组织中a-防御素和IL-1b进行了研究。方法:分别于第7天、第14天、第17天、第19天、第21天、第23天、第25天、第28天(D)对aglionness诱导大鼠和对照大鼠实施安乐死。各时间点分离乙状结肠组织，苏木精-伊红染色分析小肠结肠炎程度及Paneth细胞化生和增生，酶联免疫吸附试验(ELISA)检测a-防御素和白细胞介素(IL)-1b蛋白水平。结果:小肠结肠炎评分随时间增加而增加。D14 ~ D28时Paneth细胞化生、增生(p<0.01)， IL-1b水平升高。a-防御素蛋白表达水平最初升高(D7-D14;与对照组相比，p<0.01)，但在D19至D28之间呈反向变化(与D7和D14相比，p<0.01)。小肠结肠炎程度与乙状结肠Paneth细胞数量呈正相关(r=0.42)。结论:Paneth细胞在HSCR大鼠乙状结肠发生化生和增生，与小肠结肠炎程度的增加相对应，但并未随之出现a-防御素和IL-1b水平的升高，提示Paneth细胞参与了HSCR所致小肠结肠炎的病理生理过程。关键词:巨结肠，小肠结肠炎，防御蛋白;化生，潘氏细胞，动物模型

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The Indonesian Biomedical Journal

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