AUTHOR=Gao Lin , Zhao Huiru , Zhu Tao , Liu Yeliu , Hu Li , Liu Zhenguo , Huang Hai , Chen Fuxue , Deng Zhenxu , Chu Dechang , Du Dongshu 

TITLE=The Regulatory Effects of Lateral Hypothalamus Area GABAB Receptor on Gastric Ischemia-Reperfusion Injury in Rats

JOURNAL=Frontiers in Physiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00722

DOI=10.3389/fphys.2017.00722

ISSN=1664-042X

ABSTRACT=<p><bold>HIGHLIGHTS</bold><list list-type="bullet"><list-item><p>The aim of the research was to determine the functional effects and molecular mechanisms of GABA<sub>B</sub> receptor on ischemia reperfusion-induced gastric injury in rats.</p></list-item><list-item><p>The lateral hypothalamus area GABA<sub>B</sub> receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABA<sub>B</sub>R, and down-regulating <italic>P-</italic>GABA<sub>B</sub>R in the brain.</p></list-item><list-item><p>This work would provide a new therapeutic strategy for acute gastric injury.</p></list-item></list></p><p>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<sub>B</sub> receptor (GABA<sub>B</sub>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 <italic>L-</italic>Glu was microinjected into FN, GABA<sub>B</sub> receptor agonist baclofen, or GABA<sub>B</sub> receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABA<sub>B</sub>R, <italic>P</italic>-GABA<sub>B</sub>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 <italic>L-</italic>Glu into the FN or GABA<sub>B</sub> receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABA<sub>B</sub> 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.</p><p><bold>Conclusion:</bold> The protective effects of microinjection of GABA<sub>B</sub>R agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABA<sub>B</sub>R, and down-regulating <italic>P</italic>-GABA<sub>B</sub>R in the LHA.</p>