下丘脑腹内侧核Orexin-1及其受体对大鼠胃酸分泌的影响及其机制

目的:探讨下丘脑腹内侧核Orexin-1及其受体对大鼠胃酸分泌的影响及其机制。方法:大鼠麻醉后侧脑室及VMH置管,大鼠分组后分别VMH注射orexin-A、Pro~(34)]-酪酪肽、c PP1-7、NPY~(19-23)、Ala~(31)、Aib~(32)、Gln~(34)]胰多肽;腹腔注射SB-334867;皮下注射阿托品;侧脑室微量注射GR-231118、CGP-71683。给药结束后使用幽门结扎模型检测大鼠的胃酸分泌。结果:OXA能够促进胃酸分泌,且呈量效依赖关系。腹腔注射SB-334867能够抑制胃酸分泌,且呈量效依赖关系;SB-334867能够抑制orexin-A对胃酸分泌的促进作用;阿托品不但能够抑制胃酸分泌并且还能够完全阻断OXA的促胃酸分泌作用。侧脑室微量注射GR-231118或CGP-71683胃酸及胃液量减少,呈量效依赖关系,并且能够完全阻断OXA的促胃酸分泌作用。VMH内微量注射cPP~(1-7),NPY~(19-23),Ala~(31),Aib~(32),Gln~(34)]胰多肽胃酸分泌增多,且呈量效依赖关系。结论:Orexin-A能够作用于下丘脑VMH促进胃酸分泌,orexin受体、Y1和Y5受体以及迷走神经系统均参与该过程。

Role of the Ventromedial Hypothalamic Orexin-1 and Orexin-1 Receptors in Regulation of Gastric Acid Secretion in Conscious Rats

ABSTRACT Objective: This study aimed to explore the Ventromedial Hypothalamic Orexin-1 and Orexin-1 Receptors in Regulation of Gastric Acid Secretion in Conscious Rats. Methods: Rats were anaesthetized and fitted with a stainless steel cannula placed just above the VMH or paracele, after random allocation orexin-A, Pro³⁴] - peptide YY and CPP^1-7, NPY^19-23, Ala³¹, Aib³², Gln³⁴]-pancreatic polypeptide were injected in the VMH; SB-334867 was intraperitoneal injection; atropine was subcutaneous injection; GR-231118 and CGP-71683 were injected in the paracele. Using pyloric ligation model, tests the effect of different drugs on rat gastric acid secretion and gastric juice volume. Results: OXA induced dose-dependent increase of gastric acid secretion; SB-334867 induced dose-dependent inhibition of gastric acid secretion. The stimulatory effect of OXA on acid secretion was inhibited by SB-334867; atropine induced dose-dependent increase of gastric acid secretion and block the effect of orexin-A on gastric acid secretion; the gastric acid secretion was inhibited by GR-231118 or CGP-71683, and GR-231118 or CGP-71683 were blocked the effect of orexin-A on gastric acid secretion; Intraventromedial hypothalamic injections of CPP^1-7, NPY^19-23, Ala³¹, Aib³², Gln³⁴]-pancreatic polypeptide increased gastric acid secretion. Conclusion: It is suggested that endogenous orexin-A acts on the ventromedial hypothalamus to stimulates acid secretion. This stimulatory effect is probably mediated through orexin receptor, Y1 and Y5 receptor, and the vagus nerve system.