Ghrelin对糖尿病大鼠下丘脑弓状核胃扩张敏感神经元和胃运动的影响

目的:探讨Ghrelin对糖尿病大鼠下丘脑弓状核胃扩张敏感神经元和胃运动的影响。方法:逆行追踪结合免疫组化观察ARC中GHSR-1的表达,细胞外放电记录,观察ghrelin对GD神经元放电活动的影响及电刺激ARC对GD神经元放电活动和胃运动的影响。结果:电生理实验结果表明,在ARC Ghrelin能够能激发GD兴奋性神经元(GD-E)和GD抑制性神经元(GD-I)。然而,ghrelin可以兴奋更少的GD-E神经元,在正常大鼠中ghrelin对于GD-E的兴奋作用比在DM大鼠中的作用弱。在体胃运动研究表明,在ARC中微量注射ghrelin可以明显的增强胃运动,并且呈现剂量依赖关系。Ghrelin在糖尿病大鼠促胃动力作用低于正常大鼠。Ghrelin诱导的效应可被生长激素促分泌素受体(GHSR)拮抗剂阻断[d-lys-3]-GHRP-6或bim28163。放射免疫法和实时荧光定量PCR数据表明胃血浆ghrelin水平,在ARC ghrelin mRNA的表达水平先上升后下降,糖尿病大鼠(DM)中,在ARC中GHSR-1a mRNA表达保持在一个比较低的水平。结论:ghrelin可以调节GD敏感神经元以及胃运动,通过ARC中ghrelin受体。在糖尿病大鼠中,Ghrelin促进胃运动作用减弱可能与ARC中ghrelin受体表达减少有关。

Effect of Ghrelin on Hypothalamic Arcuate Nucleus Gastric Stretch Sensitive Neurons and Gastric Motility in Diabetic Rats

ABSTRACT Objective: To investigate the effect of Ghrelin on gastric diabetic rat hypothalamic arcuate nucleus expansion sensitive neurons and gastric motility. Methods: Retrograde tracing combined with immunohistochemistry to observe the expression of ARC in GHSR-1, extracellular discharge records, the effect of ghrelin effect on the firing activities of GD neurons and GD neurons to electrical stimulation of the ARC activity and gastric motility. Results: electrophysiological experiments showed that ARC Ghrelin could stimulate GD excitatory neurons (GD-E) and GD inhibitory neurons (GD-I). However, ghrelin could be less excited by GD-E neurons, and the effect of ghrelin on GD-E in normal rats was weaker than that in DM rats. In vivo gastric motility studies showed that microinjection of ghrelin into ARC significantly enhanced gastric motility and showed dose-dependent. The effect of Ghrelin on gastric motility in diabetic rats was lower than that in normal rats. Ghrelin induced effects may be blocked by the growth hormone receptor (GHSR) antagonist (d-lys-3) - GHRP-6 or bim28163. Radioimmunoassay and quantitative real-time PCR data showed that gastric plasma ghrelin levels increased in the expression level of ARC ghrelin decreased after mRNA, diabetic rats (DM), in ARC GHSR-1a mRNA expression remained at a relatively low level. Conclusion: Ghrelin can regulate GD sensitive neurons and gastric motility via ghrelin receptor in ARC. In diabetic rats, Ghrelin may be associated with decreased expression of ghrelin receptor in the gastric mucosa by ARC.