Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice
Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice
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DOI：
10.1016/s0016-5085(98)70259-8
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发表时间：
1998-10-01
期刊：
影响因子：
29.4
通讯作者：
Stenson, WF
中科院分区：
文献类型：
--
作者：
Tessner, TG;Cohn, SM;Stenson, WF
背景和目标：虽然葡聚糖硫酸钠（DSS）诱导的结肠炎是一种常用的结肠损伤模型，但该模型的机制尚不清楚。本研究的目的是确定洋地黄素的DSS诱导的上皮损伤的机制的贡献。方法：小鼠饮用含3% DSS的水，连续5天，然后只饮水（恢复期）。检测组织中前列腺素E2（PGE 2）水平，溴脱氧尿苷标记法检测盲肠隐窝增殖细胞数，免疫组化法检测环氧化酶（考克斯）1和考克斯2的细胞定位。结果如下：DSS使每个隐窝的增殖上皮细胞数量减少约90%，盲肠隐窝高度降低40%。DSS与二甲基PGE（2）联合给药可逆转DSS对增殖的影响，但不能逆转其对隐窝缩短的影响。考克斯-1在隐窝上皮和固有层单核细胞中表达; DSS处理仅下调上皮中的考克斯-1表达。二甲基PGE（2）可逆转DSS对考克斯1表达的影响。恢复与上皮中恢复正常的考克斯-1表达相关，考克斯-2在固有层单核细胞中表达。结论：DSS存在时上皮细胞增殖包含PGE（2）敏感成分。
Background & Aims: Although dextran sodium sulfate (DSS)-induced colitis is a commonly used model of colonic injury, the mechanism of this model is not understood. The aim of this study was to determine the contribution of prostaglandins to the mechanism of DSS-induced epithelial injury. Methods: Mice were treated with 3% DSS in the drinking water for 5 days followed by water only (recovery). Tissue prostaglandin E-2 (PGE(2)) levels were measured, proliferating cells per cecal crypt were determined by bromodeoxyuridine labeling, and the cellular localization of cyclooxygenase (COX)-1 and COX-2 was determined by immunohistochemistry. Results: DSS decreased the number of proliferating epithelial cells per crypt by approximately 90% and decreased the height of cecal crypts by 40%, Administration of dimethyl PGE(2) with DSS reversed the effect of DSS on proliferation but not its effect on crypt shortening. COX-1 was expressed in the crypt epithelium and lamina propria mononuclear cells; DSS treatment down-regulated COX-1 expression only in the epithelium. Dimethyl PGE(2) reversed the effect of DSS on COX-1 expression. Recovery was associated with a return to normal COX-1 expression in the epithelium, COX-2 was expressed in lamina propria mononuclear cells. Conclusions: Epithelial cell proliferation in the presence of DSS contains a PGE(2)-sensitive component.