Abstract
HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats.The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain.This work would provide a new therapeutic strategy for acute gastric injury.Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN). This study aims to investigate the protective effects of GABAB receptor (GABABR) in the lateral hypothalamic area (LHA) on GI-R injury. A model of GI-R injury was established by clamping the celiac artery for 30 min and then reperfusion for 1 h. The coordinate of FN and LHA was identified in Stereotaxic Coordinates and then the L-Glu was microinjected into FN, GABAB receptor agonist baclofen, or GABAB receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABABR, P-GABABR, NOX2, NOX4, and SOD in the LHA was detected by western blot, PCR, and RT-PCR. The expression of IL-1β, NOX2, and NXO4 in gastric mucosa was detected by western blot. We found that microinjection of L-Glu into the FN or GABAB receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa.Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.
Highlights
Many surgery-evoked ischemia have been suggested to induce gastric mucosal injury as well as gastrointestinal dysmotility (Gross and Auchampach, 2007; Tsukamoto et al, 2011)
Our previous studies showed that chemical stimulation of fastigial nucleus (FN) with L-Glu attenuated gastric ischemia- reperfusion injury, microinjection of GABAA receptor antagonist into lateral hypothalamic area (LHA) aggravated Gastric ischemia-reperfusion (GI-R) injury (Du et al, 2013), cerebellar-hypothalamic circuits modulate the gastric mucosal injury induced by ischemia-reperfusion
We found that unilateral microinjection of GABAB receptor agonist baclofen into the LHA attenuated GI-R injury
Summary
Many surgery-evoked ischemia have been suggested to induce gastric mucosal injury as well as gastrointestinal dysmotility (Gross and Auchampach, 2007; Tsukamoto et al, 2011). Z. et al, 2012) are three major nuclei that can regulate gastric activity and gastric mucosal injury in GI-R model. Our previous studies showed that chemical stimulation of FN with L-Glu attenuated gastric ischemia- reperfusion injury, microinjection of GABAA receptor antagonist into LHA aggravated GI-R injury (Du et al, 2013), cerebellar-hypothalamic circuits modulate the gastric mucosal injury induced by ischemia-reperfusion. A recent study indicated that GABAA receptor overexpression in the LHA attenuated gastric ischemia-reperfusion injury in rats (Gao et al, 2015)
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