The Regulatory Effects of Lateral Hypothalamus Area GABA(B) Receptor on Gastric Ischemia-Reperfusion Injury in Rats

HIGHLIGHTS: The aim of the research was to determine the functional effects and molecular mechanisms of GABA(B) receptor on ischemia reperfusion-induced gastric injury in rats. The lateral hypothalamus area GABA(B) receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABA(B)R, and down-regulating P-GABA(B)R 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 GABA(B) receptor (GABA(B)R) 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, GABA(B) receptor agonist baclofen, or GABA(B) receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABA(B)R, P-GABA(B)R, 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 GABA(B) receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABA(B) 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 GABA(B)R agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABA(B)R, and down-regulating P-GABA(B)R in the LHA.