大鼠海马CA1区-杏仁核大麻素受体信号通路对糖尿病大鼠摄食及胃运动的影响

Influence of CA1 Region of Hippocampus and Amygdaloid Nucleus Cannabinoid Receptor Signaling Pathway on Feeding and Gastric Motility in Diabetic Rats

目的:本实验主要探究了大鼠海马CA1区-杏仁核(BMA)大麻素受体信号通路对糖尿病大鼠摄食及胃运动的影响。方法:通过免疫组织化学染色方法确定大鼠海马CA1区是否表达大麻素受体,以及海马CA1区-BMA是否存在纤维投射;通过向大鼠海马CA1区注射大麻素、大麻素受体拮抗剂利莫那班(Rimonabant)及GLP-1受体激动剂Exendix-4,测定大鼠0~4h及4~8h摄食量改变,以及对胃运动的影响;观察大麻素及GLP-1受体激动剂Exendix-4对糖尿病大鼠胃牵张(GD)敏感神经元放电活动的影响。结果:免疫组织化学染色结果证实了海马CA1区存在大麻素受体,且海马CA1区-BMA之间存在纤维投射;通过向大鼠海马CA1区注射大麻素、大麻素受体拮抗剂Rimonabant及GLP-1受体激动剂Exendix-4能够减少食物摄入并抑制大鼠胃运动;海马CA1区微量注射大麻素后,正常大鼠GD敏感神经元放电频率显著增加,该效应可被大麻素受体拮抗剂Rimonabant完全阻断,Exendix-4可部分阻断大麻素的促放电效应;与正常大鼠相比,海马CA1区微量注射大麻素后糖尿病大鼠GD敏感神经元放电频率均显著增加(P<0.05);海马CA1区微量注射大麻素后,大鼠胃运动幅度和频率均显著增加,但糖尿病大鼠胃运动增加更加显著。结论:大鼠海马CA1区存在大麻素受体,且海马CA1区-BMA大麻素受体信号通路参与调节大鼠摄食及胃运动。

Objective:To explore the influence of cannabinoid receptor signaling pathway in rat hippocampal CA1 area-amygdala(BMA) on feeding and gastric motility in diabetic rats.Method:Immunohistochemical staining was used to observe whether the cannabinoid receptor was expressed in the hippocampal CA1 region and whether there was fiber projection from the hippocampal CA1 region to the BMA.The cannabinoid,cannabinoid receptor antagonist Rimonabant and GLP-1 receptor agonist Exendix-4 were injected into the hippocampal CA1 region of rats to determine the food intake during 0-4 h and 4-8 h,and the effects on gastric motility.Administrated cannabinoids and GLP-1 receptor agonist Exendix-4 into the hippocampal CA1 area to observe the effects of gastric distraction(GD)-sensitive neurons in diabetic rats.Result:Immunohistochemical staining showed that cannabinoid receptors expressed in the hippocampal CA1 region,and there was fiber projection from the hippocampal CA1 region to the BMA.Administrated cannabinoids and the GLP-1 receptor agonist Exendix-4 into the hippocampal CA1 region of rats could reduce food intake and inhibit gastric motility in rats.After microinjection of cannabinoids in the hippocampal CA1 area, the discharge frequency of GD-sensitive neurons in normal rats increased significantly.This effect was completely blocked by the cannabinoid receptor antagonist Rimonabant,and Exendix-4 partially blocked the promoting discharge effect of cannabinoids.Compared with normal rats,the discharge frequency of GD-sensitive neurons in diabetic rats was significantly increased after microinjection of cannabinoids in hippocampal CA1 area(P<0.05).After microinjection of cannabinoids in the hippocampal CA1 area,the amplitude and frequency of gastric motility in rats increased significantly,but the diabetic rats gastric motility was increase more significant.Conclusion:Cannabinoid receptors are expressed in the hippocampal CA1 region of diabetic rats,and the hippocampal CA1 region-BMA cannabinoid receptor signaling pathway is involved in the regulation of feeding and gastric motility in rats.