Molecular mechanisms of Wischnewski spot development on gastric mucosa in fatal hypothermia: an experimental study in rats
Molecular mechanisms of Wischnewski spot development on gastric mucosa in fatal hypothermia: an experimental study in rats
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DOI：
10.1038/s41598-020-58894-8
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发表时间：
2020-02-05
影响因子：
4.6
通讯作者：
Matsumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Yang, Chihpin;Sugimoto, Kana;Matsumoto, Hiroshi
在死于体温过低的患者的胃粘膜中，经常可以观察到许多深棕色的小斑点，称为“Wischnewski斑点”，但这些斑点形成的分子机制尚不清楚。我们推测，低温可能会激活胃酸和胃酶的分泌，导致斑点的形成。为了研究这一点，我们使用37摄氏度(对照组)或32摄氏度(冷)培养的器官型大鼠胃组织切片进行了实验。冷负荷6h可降低培养基胞外pH。冷负荷3h后，调节胃酸分泌的胃泌素基因表达增加。冷负荷使胃尖小管膜H+，K+-ATPase泵蛋白表达增加，壁细胞形态发生动态变化。冷负荷导致胃蛋白酶C蛋白丰度增加，其前体孕激素的mRNA表达增加。总之，我们的发现阐明了冷应激通过激活胃H+，K+-ATPase泵而诱导酸化，并通过诱导胃粘膜上的孕激素表达促进胃蛋白酶C的释放，导致胃粘膜的微小出血或侵蚀，在致命低温下表现为Wischnewski斑点。
Numerous dark-brown-coloured small spots called "Wischnewski spots" are often observed in the gastric mucosa in the patients dying of hypothermia, but the molecular mechanisms through which they develop remain unclear. We hypothesised that hypothermia may activate the secretion of gastric acid and pepsin, leading to the development of the spots. To investigate this, we performed experiments using organotypic rat gastric tissue slices cultured at 37 degrees C (control) or 32 degrees C (cold). Cold loading for 6h lowered the extracellular pH in the culture medium. The mRNA expression of gastrin, which regulates gastric acid secretion, increased after cold loading for 3h. Cold loading increased the expression of gastric H+,K+-ATPase pump protein in the apical canalicular membrane and resulted in dynamic morphological changes in parietal cells. Cold loading resulted in an increased abundance of pepsin C protein and an elevated mRNA expression of its precursor progastricsin. Collectively, our findings clarified that cold stress induces acidification by activating gastric H+,K+-ATPase pumps and promoting pepsin C release through inducing progastricsin expression on the gastric mucosa, leading to tiny haemorrhages or erosions of the gastric mucosa that manifest as Wischnewski spots in fatal hypothermia.