Cutaneous burn increases apoptosis in the gut epithelium of mice.
Cutaneous burn increases apoptosis in the gut epithelium of mice.
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DOI：
10.1016/s1072-7515(98)00260-9
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发表时间：
1999
影响因子：
5.2
通讯作者：
S. Wolf;Hiroto Ikeda;S. Matin;M. Debroy;Srinivasan Rajaraman;D. N. Herndon;James C. Thompson
中科院分区：
文献类型：
--
作者：
S. Wolf;Hiroto Ikeda;S. Matin;M. Debroy;Srinivasan Rajaraman;D. N. Herndon;James C. Thompson
背景：肠道黏膜稳态依赖于细胞增殖和细胞死亡之间的平衡。皮肤烧伤后，肠黏膜重量下降。体重的减少与肠道增殖因子的增加矛盾地相关。为了使粘膜重量在增殖增加的情况下减少，细胞死亡必须有更大的增加。我们假设皮肤烧伤主要通过细胞凋亡导致肠道上皮细胞死亡增加。研究设计：我们在麻醉的雄性C57BL6小鼠背部制造30%全层烫伤，并在损伤后12、24、36、48和60小时收集近端小肠。假烧伤的动物作为对照。细胞凋亡和细胞增殖通过免疫组化检测（末端脱氧尿苷镍端标记细胞凋亡和增殖细胞核抗原检测细胞增殖）。细胞凋亡也通过ELISA检测细胞质组蛋白相关DNA片段。在组织学切片上测定粘膜高度。两组在每个时间点采用Wilcoxon双样本检验和t检验进行比较，适当时采用Bonferroni校正。结果：损伤后12、24、48小时，绒毛细胞凋亡百分率（每100个绒毛细胞用末端脱氧尿苷镍端标记染色的细胞数）显著升高。12小时时ELISA升高证实了这一增加。增殖细胞核抗原免疫染色测定增殖在12、24、48和60小时显著增加。作为衡量粘膜萎缩的大体指标，粘膜高度在两组间无显著差异。结论：我们已经证明，烧伤后细胞凋亡增加，同时细胞增殖增加。这些结果表明，烧伤后肠道上皮细胞的细胞更新增加。烧伤后反复出现肠功能受损，这可能与细胞更新的增加有关。
Background:Gut mucosal homeostasis depends on a balance between cell proliferation and cell death. After cutaneous burn injury, gut mucosal weight has been shown to decrease. This decrease in weight was paradoxically associated with an increase in gut proliferative factors. For mucosal weight to decrease in the presence of increased proliferation, there must be an even greater increase in cell death. We postulate that cutaneous burn injury causes an increase in gut epithelial cell death primarily by apoptosis.Study Design:We produced a 30% full-thickness scald burn in the dorsum of anesthetized male C57BL6 mice and collected the proximal small bowel at 12, 24, 36, 48, and 60 hours after injury. Sham burned animals served as controls. Apoptosis and proliferation were measured by immunohistochemical assays (terminal deoxyuridine nick-end labeling for apoptosis and proliferative cell nuclear antigen assay for proliferation). Apoptosis was also measured by ELISA for cytoplasmic histone-associated DNA fragments. Mucosal height was determined on histologic sections. The two groups were compared at each time point using Wilcoxon two-sample test and t-test with Bonferroni’s correction where appropriate.Results:The percentage of apoptotic cells (number of cells stained by terminal deoxyuridine nick-end labeling per 100 villus cells) was significantly higher at 12, 24, and 48 hours after injury. This increase was corroborated by an increase in the ELISA at 12 hours. Proliferation as measured by immunostaining for proliferative cell nuclear antigen significantly increased at 12, 24, 48, and 60 hours. Mucosal height as a gross measure of mucosal atrophy was not different between the groups.Conclusions:We have shown an increase in apoptosis coupled with an increase in proliferation after a burn injury. These results imply an increase in cell turnover in the gut epithelial cells after a burn. Impaired bowel function has been demonstrated repeatedly after burn injury, and this increase in cell turnover may be related.