Ghrelin对糖尿病小鼠胃排空的影响及机制

Effect of ghrelin on gastric emptying in diabetic mice and its mechasnism

目的:探讨ghrelin对糖尿病小鼠胃排空的影响及其作用机制.方法:采用四氧嘧啶建立糖尿病小鼠模型,用灌食phenol red的方法研究糖尿病小鼠胃排空的改变,并观察注射不同剂量ghrelin(50,100和200μg/kg)对糖尿病小鼠胃动力的影响.糖尿病小鼠胃底环形平滑肌条安置在恒温灌流肌槽中并用SMUP-E生物信号处理系统记录肌条的自发收缩活动,观察不同浓度ghrelin(0.1,1和10μmol/L)对肌条自发收缩活动的影响,并研究其作用机制.结果:糖尿病小鼠的胃排空率显著低于正常小鼠的胃排空率(22.90%±1.42% vs 28.10%±1.28%,P<0.05).ghrelin能显著提高糖尿病小鼠的胃排空,具有明显的量效关系.Ghrelin在0.1,1和10μmol/L均能显著增加糖尿病小鼠离体胃底环形平滑肌肌条的自发收缩幅度(1.11±0.03,1.22±0.02,1.36±0.04 vs 1.00,均P<0.05),而atropine和L-NAME均能抑制ghrelin增加糖尿病小鼠肌条自发收缩幅度的效应.结论:Ghrelin能提高糖尿病小鼠的胃排空能力,作用机制可能是通过肌间丛神经系统的硝基能神经和胆碱能神经上的受体而起作用.

AIM： To investigate the gastroprokinetic effect of ghrelin in diabetic mice and its mechanism. METHODS： The effects of ghrelin （50, 100 and 200μg/kg） on gastric emptying in diabetic mice were after intragastric application of phenol red in vivo, The effects of ghrelin on the spontane-ous contraction of fundic stomach muscle strips in the presence of ghrelin on the spontaneous contraction of fundic muscle strips from the stomachs of diabetic mice were studied in vitro, The effects of atropine and NG-nitro-L-arginine methyl ester hydrochloride （L-NAME） were also investigated. RESULTS： Ghrelin accelerated gastric emptying in diabetic mice with a significant dose-response relationship, Administration of ghrelin to tissue increased the spontaneous contraction of fundic stomach muscle strips from diabetic mice （1.11±0.03, 1.22±0.02, 1.36±0.04 vs 1.00, all P 〈 0.05）, In the presence of atropine or L-NAME, ghrelin failed to increase the spontaneous contraction of these strips CONCLUSION： Ghrelin can accelerate gastric emptying in diabetic mice, perhaps by activating the GHS-R cholinergic excitatory pathways and nitrergic nervous pathways in the enteric ner- vous system.