Abstract
Different kinds of factors contribute to gastric ulcer development which characterized by damaging gastric mucosal layer. However, gastric vascular homeostasis is not well defined and whether andrographolide has a protective function is largely unknown. The goal of this study is to investigate the potential function roles and underlying mechanism by which andrographolide regulates gastric vascular homeostasis in vivo and in vitro. Gastric ulcer animal model induced on andrographolide pretreated C57/BL6 mouse by ethanol intragastric administration. Hematoxylin and Eosin Stain, Masson’s trichrome stain and Immunohistochemistry stain performed to observe gastric vascular homeostasis, which associated hemorrhage, extracellular matrix deposition and macrophage infiltration. The activity of vascular endothelial cells were associated with the proliferation and migration, which were detected using cell counting, MTS, and wound scratch healing assay. The underlying endothelial glycolytic mechanism investigated in vivo and in vitro. Andrographolide pretreatment dramatically attenuates ethanol intragastric administration induced imbalance of gastric vascular homeostasis which characterized by severe hemorrhage, increase extracellular matrix deposition and augment macrophage infiltration. Andrographolide treatment conspicuous inhibits HUVEC-C activity characterized by suppressing proliferation and migration of endothelial cells. Mechanically, andrographolide treatment significant suppresses the expression of glycolytic genes, especially decrease PFKFB3 expression. The treatment with PFKFB3 inhibitor, 3-PO, exacerbates the inhibitory function of andrographolide on vascular endothelial cell proliferation and migration. Those data Suggests that andrographolide contributes to maintain gastric vascular homeostasis, at least partially, by inhibiting PFKFB3 mediated glycolysis pathway. Andrographolide plays a crucial role in maintaining gastric vascular homeostasis during gastric ulcer development through regulating vascular endothelial cell glycolytic pathway.
Highlights
Gastric ulcer is open scores developed inside lining of stomach characterized by burning pain
A number of factors contributes to gastric ulcer development have been defined, such as bacterial helicobacter pylori infection, drug abuse, endocrine dyscrasia, heavy drinking and so on, which impairs mucosal barrier through disturbing gastric acid secretion characterized by hemorrhage and serious inflammatory response[32,33]
We observed severe hemorrhage within submucosal layer with intact mucosal layer, as well as abundant macrophage infiltration (Fig. 6A). Those data suggests, except damage of mucosal layer, inflammatory cells infiltration from circulation due to vascular homeostasis impairment contribute to gastric ulcer development
Summary
Gastric ulcer is open scores developed inside lining of stomach characterized by burning pain. The underlying mechanism for gastric ulcer development still poorly understood. One common factor contributes to the development of gastric ulcer is infected by bacterial helicobacter pylori[1]. Whether the vascular system homeostasis within mucosal layer is essential for gastric ulcer development is unclear. Ethanol intragastric administration induced Gastric ulcer animal model has been widely used to explore the underlying mechanism for gastric ulcer development[17]. Ethanol intragastric administration causes mucosal damage[18,19], as well as serious inflammatory response[20]. Whether ethanol induced gastric inflammation through impairing endothelial regulated vascular homeostasis still poorly understood. Whether glycolytic pathway contributes to maintain gastric vascular homeostasis in a gastric ulcer animal model induced by ethanol intragastric administration is remain unknown
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