目的了解电刺激大鼠下丘脑室旁核(PVN)对海马CA1区ghrelin调控胃扩张(GD)敏感神经元放电活动的影响,初步探讨ghrelin在PVN-海马通路中的调控作用。方法选用成年Wistar大鼠84只,采用电刺激PVN、核团微量注射及细胞外记录神经元单位放电方法,记录电刺激PVN海马CA1区GD敏感神经元自发放电活动的改变;同时观察海马CA1区给予ghrelin受体阻断剂[D-Lys-3]-GHRP-6,海马CA1区GD敏感神经元放电活动的变化。结果海马CA1区记录的255个神经元中有120个(47.1%)神经元对GD刺激有反应,其中84个(70.0%)为GD兴奋性(GD-E)神经元,36个(30.0%)为GD抑制性(GD-I)神经元。在GD-E神经元中,微量注射ghrelin可兴奋其中53.1%的神经元,与核团注射生理盐水组相比,放电频率显著增加(t=2.686,P〈0.05);而在GD-I神经元中,微量注射ghrelin后58.3%神经元呈抑制效应,放电频率显著降低(t=3.591,P〈0.05),且ghrelin的效应可被其受体阻断剂[D-Lys-3]-GHRP-6完全阻断。对ghrelin有兴奋反应的GD-E神经元,电刺激PVN,其中23.5%GD-E神经元的兴奋效应可被[D-Lys-3]-GHRP-6部分阻断。结论 PVN可调控海马CA1区GD敏感神经元放电活动,在PVN-海马直接或间接通路中ghrelin参与了兴奋传递的调控。
Objective To explore the effects of electrical stimulation of hypothalamic paraventricular nudes (PVN) in rats on the activity of ghrelin regulation of gastric distention (GD) sensitive neurons in the hippoeampal CA1 region, and prelimina- rily study the regulation of ghrelin in the PVN-hippocampal pathway. Methods Eighty-four adult Wistar rats were selected in this experiment. The effects of electrical stimulation of PVN on the activity of GD sensitive neurons in the hippocampal CA1 region were observed by electrical stimulation of PVN, nuclei microinjecion and recording extracellular potentials of single neuron. The changes of the GD sensitive neurons discharge activities in the hippocampal CA1 area were also observed while administration of ghrelin receptor antagonist ghrelin-[D-Lys-3]-GHRP-6. Results In the hippocampal CA1 region, 255 neurons were recorded, of which,120 (47.1%) responded to GD stimulation. Of the 120 GD responsive neurons, 84 (70.0%) were GD-excitatory (GD-E) neurons and 36 (30.0%) were GD-inhibitory (GD-I) neurons. Microinjection of ghrelin excited 53.1% of 84 GD-E neurons, and compared with the control group, the discharge frequency significantly increased (t = 2. 686, P d0.05); Microinjection of ghrelin inhibited 58.3 % of neurons and the discharge frequency reduced (t = 3. 591, P d0.05), the effect of ghrelin could be completely blocked by antagonist of ghrelin-[D-Lys-3]-GHRP-6. Among GD-E and GD-I neurons that were excited by ghrelin, 23.5% of OD- E excited effect could be partially blocked by [D-Lys-3]-GHRP-6. Conclusion PVN can regulate the activity of GD sensitive neurons in the hippocampal CA1 region and ghrelin is involved in the regulation of excitement transfer through direct or indirect PVN-hippocampus pathway.