| Objective:To explore the changes of activity of gastric distention (GD) sensitive neurons of hypothalamic arcuate nucleus (Arc) in diabetes mellitus (DM) rat model, and to study the effects of Ghrelin on gastric distention neurons in hypothalamic arcuatus nucleus in DM rat; To study the effect of Ghrelin microinjected into hypothalamic arcuatus nucleus (Arc) on gastric motility in rat with diabetic Gastroparesis (DGP).Method:DM rat model was made by intraperitoneal injection of streptozotocin (STZ). The effects of Ghrelin and D-Lys-3-GHRP-6on GD sensitive neurons of Arc in DM rats were observed by recording extracellular potentials of single neurons. The fluorescent immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Real-time quantitative Polymerase Chain Reaction (real-time PCR) were performed to evaluate the protein and mRNA expression of Ghrelin receptor (GHS-R) in Arc of rats with Diabetes. Gastric motility was recorded to observe the effect of Ghrelin injection into Arc on the diabetic rats.Results:(1) The ratio of neither GD-E nor GD-I neurons changed in Arc of diabetic rats (t=0.89, t=1.04, P>0.05). However, the ratio of GD-E neurons significantly decreased by Ghrelin administration (X2=3.86, P<0.05), and the average increase rate of discharge frequency was significantly decreased (t=2.02, P<0.05). Comparing with normal rats, both the inhibition ratio (X2=0.22, P>0.05) and discharge average reduction rate reduced by Ghrelin were no significantly change in GD-I neurons (t=0.15, P>0.05).(2) The number of GHS-R immunoreactive neurons and the relative volume of GHS-R mRNA in Arc of normal rats were10±2.1/mm2and0.48±0.13, while in DGP rats the numbers decreased to3±0.7/mm2and0.21±0.10(P<0.05). In normal rats the amplitude and frequency of gastric motility were8.14±1.58g and5.18±0.61/min. The microinjection of Ghrelin into the Arc increased the gastric motility dose dependently:at the12min after Ghrelin injection, the amplitude and frequency were14.6±2.2g and7.45±0.87/min (vs NS group, P<0.05) in L group or22.28±4.1gand10.98±1.03/min (vs NS group, P<0.01; vs L group. P<0.05) in H group. In DGP rats the amplitude and frequency of gastric motility were2.21±0.89g and1.81±0.2/min/min (vs NS group, P<0.05). The0.05mmol Ghrelin microinjected into the Arc of DGP rats increased the gastric motility to5.04±1.11 g and3.81±0.43/min (vs DGP+NS and DGP+L group, P<0.05).The GHS-R antagonist, D-Lys3-GHRP-6, totally blocked the effect of Ghrelin.Conclusion:The Ghrelin of hippocampus Arc could regulate the activity of GD sensitive neurons in diabetic rats, and the effects may be achieved by Ghrelin receptor. The gastric motility disorder of diabetic rats was partly caused by the decreased expression of GHS-R in the hypothalamus. Ghrelin could regulate the genesis of DGP through the GHS-R in Arc. |
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