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- Title
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.
- Authors
Zhang, Yong-Mei; Wei, Er-Qing; Li, Li; Qiao, Wei-Li; Wang, Lin; Zhang, Jian-Fu
- 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.
- Subjects
PROTEIN kinases; GASTRIC mucosa; APOPTOSIS; IMMUNOHISTOCHEMISTRY; ISCHEMIA; BLOOD circulation disorders; REPERFUSION
- Publication
Clinical & Experimental Pharmacology & Physiology, 2007, Vol 34, Issue 8, p742
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2007.04652.x