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

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.

Neuromechanism of acupuncture regulating gastrointestinal motility

“…Gastric vagal and cerebellar fastigial nuclear signals converge on glycemia-sensitive neurons of the LHA in rats[ 164 ]. Electrical and chemical stimulation of the FN had neuroprotective effects on gastric mucosal stress injury and gastric ischemia-reperfusion damage in rats, and pre-damage of the FN or LHA could eliminate the protective effect of the FN[ 165 - 169 ]. Extracellular recording results suggested that the signal of gastric distention (GD) and acupuncture at ST36 converged in the LHA and FN, and acupuncture could modulate the activities of different types of GD-sensitive neurons in the LHA and FN, indicating that the LHA-FN circuit might participate in the central integration mechanism of acupuncture’s effects on gastric function[ 170 ].…”

Autophagy‐lysosome dysfunction is involved in gastric ischemia‑reperfusion injury by promoting microglial activation in the paraventricular nucleus

“…After microinjection in PVN tissues, GI-R was performed as previously reported. [16] The celiac artery was clamped with a small vascular clamp for 30 min to induce ischemia, the clamp was then removed to allow reperfusion for 1, 3, or 6 h. Animals in the Sham group underwent an identical surgical procedure with the exception of clamping the celiac artery. At the end of the experiments, rats were anesthetized using isoflurane inhalation and then sacrificed by dislocation of the cervical vertebra.…”

“…The gastric mucosal injury index was assessed as previously described. [16] An individual lesion was limited to within the mucosal epithelium. The scores were calculated using the following criteria: 1, lesions ≤ 1 mm; 2, lesions >1 mm and ≤2 mm; 3, lesions >2 mm and ≤3 mm.…”

“…Total protein was extracted from PVN tissues and the protein levels of LC3-I, LC3-II, Beclin-1, and phosphorylated γ-aminobutyric acid B receptor (p-GABA B R) were determined according to our previously published article. [16] The primary antibodies were as follows: LC3 (#sc-398822; 1:500; Santa Cruz Biotechnology), Beclin-1 (#sc-48381; 1:1000; Santa Cruz Biotechnology), phospho-Ser923 GABA B R1 (#612-401-D54; 1:1000; Rockland Immunochemicals), and β-actin (#sc-47778; 1:1000; Santa Cruz Biotechnology).…”

The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs

“…Reduced norepinephrine and angiotensin II levels in plasma and peripheral GSN activity marked multiple ways of GABA preventing against gastric I/R injury in the study. A recent investigation [157] showed that the GABA B receptor in the LHA was involved in the protective effects on the gastric I/R injury caused by clamping the celiac artery. The administration of GABA B receptor agonist (baclofen) can significantly attenuate gastric I/R injury.…”