Extracellular Signal‐regulated Kinase Pathways May Mediate the Protective Effect of Electrical Stimulation of the Paraventricular Nucleus Against Ischaemia–reperfusion Injury of the Gastric Mucosa

Abstract

1. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in mediating the effects of electrical stimulation of the paraventricular nucleus (PVN) on apoptosis and proliferation induced by gastric ischaemia-reperfusion injury (GI/RI). 2. To investigate the effects of electrical stimulation of the hypothalamic PVN on gastric mucosal apoptosis and proliferation in response to ischaemia-reperfusion (I/R), we used a GI/RI model by clamping the coeliac artery for 30 min and then reperfusing the artery for 30 min or 1, 3 or 6 h. We used immunohistochemistry and western blotting to investigate the expression, activation and distribution of ERKs and the dynamic changes in their downstream cellular factors Bcl-2 and Bax at different times subsequent to electrical stimulation of the PVN in the I/R-injured gastric mucosa. 3. Electrical stimulation of the PVN markedly attenuated GI/RI at 30 min and 1 and 3 h after reperfusion. Electrical stimulation decreased gastric mucosal apoptosis, increased gastric mucosal proliferation and promoted the expression and activation of phosphorylated (p)-ERK1/2 30 min after reperfusion. Electrical stimulation increased the expression of Bcl-2 and decreased the expression of Bax at 30 min and 1 and 3 h after reperfusion. In contrast, inhibition of ERK1/2 activity by the specific upstream mitogen-activated protein kinase kinase inhibitor PD98059 produced similar effects at 1 h after reperfusion in rats subjected to I/R with or without electrical stimulation of the PVN. Administration of PD98059 aggravated gastric mucosal injury, increased apoptosis, decreased proliferation in gastric mucosal cells, decreased the expression and activity of p-ERK1/2 and Bcl-2 expression and increased Bax expression. 4. These results indicate that the PVN protects against GI/RI and that this protection is associated with the inhibition of cellular apoptosis and the promotion of proliferation in the gastric mucosa, probably by activating the ERK pathway.

Cellular and molecular mechanisms of 17β-estradiol postconditioning protection against gastric mucosal injury induced by ischemia/reperfusion in rats

“…According to Zhang et al (2007), the murine stomach was incised along the greater curvature and flushed with ice-cold PBS (0.1 mol/l). The index is based on a cumulative-length scale on which an individual lesion limited to the mucosal epithelium (including pinpoint erosions, ulcers, and hemorrhagic spots) is scored according to its length as follows: 1, ≤1 mm; 2, N1 mm and ≤2 mm; 3, N2 mm and ≤3 mm.…”

Protective effect of chemical stimulation of cerebellar fastigial nucleus on stress gastric mucosal injury in rats

“…Electrical and chemical stimulation of the PVN can obviously aggravate the SGMI, but markedly attenuate GI-RI (Zhang and Zheng, 1997;Zhang et al, 2002;Zhang et al, 2007). Meanwhile, it also has been founded that the electrical and chemical stimulation of LHA can aggravate GI-RI .…”

The role of nuclear factor-κB in the effect of angiotensin II in the paraventricular nucleus in protecting the gastric mucosa from ischemia-reperfusion injury in rats

“…27 Because Ang II is a stress hormone, stress increases the expression of AT1 receptors in the parvocellular PVN, 28,29 and Ang II contributes to the production of stress-induced gastric ulcerations. 30 Our previous studies 10,31,32 showed that the PVN is one of the special central nervous system areas that attenuate GI-R injury. However, whether exogenous Ang II in the PVN can regulate GI-R injury is not known, nor are its possible local molecular mechanisms.…”

“…[1][2][3][4][5][6][7][8] However, the molecular mechanisms underlying GI-R injury are not completely understood. Our previous study demonstrated that activated ERK1/2 participates in the regulation of gastric mucosal injury and repair induced by GI-R, 9,10 but the roles of nuclear factor κB (NF-κB) in the development of GI-R injury and in the protective effects of angiotensin II (Ang II) in the paraventricular nucleus (PVN) against GI-R injury need further investigation.…”