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Effect of ghrelin in septal nucleus on gastric motility of diabetic gastroparesis rats and its potential mechanism regulated by hypothalamic arcuate nucleus
Authors:YAN Chang-hong  XU Luo  GAO Sheng-li  GUO Fei-fei  SUN Xiang-rong  GONG Yan-ling
Institution:1.Department of Pathophysiology, Medical College of Qingdao University, Qingdao 266021, China;2.Heze Medical College, Heze 274000, China;3.College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Abstract:AIM:To study the effect of ghrelin in septal nucleus on the gastric motility of the rats with diabetes mellitus (DM) and to investigate the regulation of ghrelin pathway between arcuate and septal nucleus nuclei on gastric motility. METHODS:Streptozotocin was injected intraperitoneally to establish a DM rat model. Fluorescence immunohistochemistry and real-time PCR were used to detect the expression of ghrelin receptor GHS-R1a. The gastric motility was evaluated by implantation of a force transducer on the surface of rats stomachs and the motility index was also calculated. The neural connections between arcuate and septal nuclei were analyzed by the technique of fluorogold tracing. The neural control pathway of gastric motility was determined by central drug injection, nucleus lesion or nucleus electrical stimulation. RESULTS:The expression of GHS-R1a in the septal nucleus of DM rats was lower than that in normal rats (P<0.05). The amplitude and frequency of gastric motility in the DM rats were lower than those in the normal rats (P<0.05). The gastric motility of normal and DM rats were increased by injection of ghrelin into the septal nucleus in a dose-dependent manner. Seven days after injection of fluorogold into the septal nucleus, some neurons in arcuate nucleus were labeled by fluorogold and part of the labeled neurons were ghrelin immunopositive. No effect of nucleus lesion or nucleus electrical stimulation on the gastric motility in the normal rats was observed. In DM rats, the lesion of septal nucleus decreased the gastric motility (P<0.05). In the normal rats, the change of gastric motility caused by electrical stimulation in arcuate nucleus was not affected by the lesion of septal nucleus (P>0.05), while the change was attenuated in DM rats (P<0.05). The ghrelin receptor antagonist [D-Lys-3]-GHRP-6 had no significant effect on the gastric motility induced by electrical stimulation in arcuate nucleus of the normal rats (P>0.05), but it reduced the change in the DM rats (P<0.05). CONCLUSION:Ghrelin in septal nucleus and the ghrelinergic pathway between arcuate and septal nuclei play an important role in the modulation of gastric motility in DM rats.
Keywords:Diabetes Mellitus  Septal nuclei  Hypothalamus  Gastric motility  Ghrelin  
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