Study On The Constitute Of Ghrelin Pathway From The Lateral Hypothalamic Area To The Nucleus Of Solitary Tract And Its Regulation On Gastric Motilityinvomiting Rats

Objective: As a unique endogenous ligand for the growth hormone secretagogue receptor(growth hormone secretagogue receptor,GHSR),ghrelin has the function of increasing gastrointestinal motility,regulating diet and promoting growth hormone secretion.Thevomitingmodel of rats was established to investigate the constitute and alteration of the ghrelin nerve pathway from the lateral hypothalamic area(LHA)to the nucleus tractussolitarius(NTS).The effects of this pathway onthe activity of gastric distension sensitive neurons and gastric motility were also investigated.Methods: The retrograde tracing and fluorescence immunohistochemistry methods were used to investigatethe constitute of LHA-NTS ghrelin nerve pathway.The cisplatin was intraperitoneally injected to establish the vomitingmodel of rats.The changes of ghrelin and its receptor GHSR-1a were measured by ELISA,PCR and Western blot,respectively.The extracellular discharge recording and gastric motility recording methods were used to measure the effects of LHA-NTS ghrelin pathway on the discharge activities of GD neuronsand gastric motility in vomiting rats.Results: FG-positive cells,ghrelin-positive cells and double-stained cells were observed in NTS,suggesting that LHA-NTS has ghrelin nerve pathways.The concentrations of ghrelin in gastric and LHA in cisplatin-treated rats were decreased compared with saline group(P<0.05).The expression of GHSR-1a in LHA and NTS increased(P<0.05).GD sensitive neurons were recorded in the NTS of rats in two groups,and the firing frequency of GD neurons significantly increased after ghrelin injected into NTS(P<0.01).Pretreatment with [D-Lys-3]-GHRP-6 could completely block this effect.The firing frequency of ghrelin-excited GD neurons in NTS significantly increased after electrical stimulation of LHA(P<0.01),and pretreatment with [D-Lys-3]-GHRP-6 in NTS could partially block this effect.The frequency and amplitude of gastric contraction reduced after intraperitoneal injection of cisplatin(P<0.01),suggesting that cisplatin could cause the decrease of gastric motility.The amplitude and frequency of gastric contraction increased after NTS was injected of ghrelin in rats(P<0.05-0.01),and this effect could be completely blocked by [D-Lys-3]-GHRP-6.The amplitude and frequency of gastric contraction increased after electrical stimulation of LHA(P<0.01),and pre-injection of [D-Lys-3]-GHRP-6 in NTS could partially blocked this effect.The excitatory effect in cisplatin group was weaker than that in the saline group(P<0.05).Conclusions: LHA-NTS has a ghrelin neural pathway,which was involved in the regulation of gastrointestinal afferent signal and gastric motility in vomiting rats.The decrease of ghrelin secretion in LHA may lead to the destroy of ghrelin pathway in cisplatin-treated rats.The up-adaptive regulation of GHSR-1a in LHA and NTS indicates that exogenous ghrelin could relieve the symptoms which induced by cisplatin.