Background The restraint water immersion stress (RWIS) model includes both psychological and physical stimulation, which may lead to gastrointestinal disorders and cause gastric mucosal damage. The ventrolateral periaqueductal gray (VLPAG) contributes to gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported. Methods The expression of glial fibrillary acidic protein, neuronal c-Fos, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG after RWIS was assessed using western blotting and immunocytochemical staining methods. Lateral ventricle injection of astrocytic toxin L-a-aminoadipate and treatment with extracellular signal-regulated kinase (ERK)1/2 signaling pathway inhibitor PD98059 were further used to study protein expression and distribution in the VLPAG after RWIS. Results The expression of c-Fos, glial fibrillary acidic protein, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG significantly increased following RWIS and peaked at 1 hour after RWIS. Lateral ventricle injection of the astrocytic toxin L-a-aminoadipate significantly alleviated gastric mucosal injury and decreased the activation of neurons and astrocytes. Treatment with the ERK1/2 signaling pathway inhibitor PD98059 obviously suppressed gastric mucosal damage as well as the RWIS-induced activation of neurons and astrocytes in the VLPAG. Conclusions These results suggested that activation of VLPAG neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may play a critical role in RWIS-induced gastric mucosa damage.

中文翻译：

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腹外侧导水管周围灰质中的神经元和星形胶质细胞通过 ERK1/2 信号通路抑制水浸应力诱导的胃粘膜损伤

背景 约束性浸水应激（RWIS）模型包括心理刺激和生理刺激，可能导致胃肠道疾病和胃黏膜损伤。腹外侧导水管周围灰质（VLPAG）有助于胃肠功能，但它是否参与 RWIS 诱导的胃黏膜损伤尚未见报道。方法采用western blotting和免疫细胞化学染色方法评估RWIS后VLPAG中胶质原纤维酸性蛋白、神经元c-Fos和磷酸化胞外信号调节激酶1/2的表达。侧脑室注射星形胶质细胞毒素 La-氨基己二酸并用细胞外信号调节激酶 (ERK)1/2 信号通路抑制剂 PD98059 治疗进一步用于研究 RWIS 后 VLPAG 中的蛋白质表达和分布。结果 RWIS后VLPAG中c-Fos、胶质纤维酸性蛋白和磷酸化胞外信号调节激酶1/2的表达显着增加，并在RWIS后1小时达到峰值。侧脑室注射星形胶质细胞毒素 La-氨基己二酸可显着减轻胃粘膜损伤并降低神经元和星形胶质细胞的活化。用 ERK1/2 信号通路抑制剂 PD98059 治疗明显抑制胃粘膜损伤以及 RWIS 诱导的 VLPAG 中神经元和星形胶质细胞的活化。