Protective effect of carbachol postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells

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• 作者：Hongxia Han^a ; ¹ ; Jun Yang^a ; ¹ ; Sujuan Fei^a ; ^{feisj99@xzmc.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Zhangbo Liu^a ; Shengping Zhu^a ; Qiuju Dong^a ; Zhifeng Gao^a ; Shihui Wang^a ; Jianfu Zhang^b ; ^{jfzhang@xzmc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Carbachol postconditioning (CAR-P) ; Human gastric epithelial cells (hGES-1) ; Hypoxia/reoxygenation (H/R) ; Cholinergic muscarinic receptor
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：144
• 期：Complete
• 页码：234-242
• 全文大小：1453 K

文摘

We investigated the protective effects of carbachol postconditioning (CAR-P) on acute gastric mucosal injury induced by hypoxia/reoxygenation (H/R) and its possible mechanisms.

Main methods

Cell viability was detected by methyl thiazolyl tetrazolium (MTT). The apoptotic cells were examined by Hoechst 33258 staining. Flow cytometric analysis, lactate dehydrogenate (LDH) release assay, immunocytochemistry, and western blotting were used to investigate the effects of CAR-P on acute gastric mucosal injury induced by H/R. The model of H/R was established by hypoxia induction(94% N₂ + 1% O₂ + 5% CO₂ for 2 h) and reoxygenation (normoxic condition for 4 h, 8 h and 16 h).

Key findings

Our study observed the protective effect of carbachol postconditioning on H/R-induced injury in human gastric epithelial cell lines (hGES-1) cells, which is achieved by direct activation of vanilloid receptor subtype 1 (VR1) and production of calcitonin gene-related peptide (CGRP), and in the inhibition of cell apoptosis. In the study, we demonstrate that CAR-P has protective effects on the H/R-induced injury in hGES-1 cells, and these effects are associated with cholinergic muscarinic receptors (CMR), VR1, and extracellular signal-regulated kinase (ERK) signaling pathway.

Significance

Our findings might provide a new and improved understanding of CAR-P function and an effective treatment strategy for acute gastric mucosal injury induced by H/R.