生长激素释放肽ghrelin对小鼠结肠动力的影响

目的 探讨生长激素促分泌素受体(growth hormone secretagogue receptor,GHSR)内源性激动剂生长激素释放肽ghrelin对小鼠结肠动力的影响.方法 小鼠按随机数字法分组后,分别注射生理盐水和不同剂量ghrelin(20,50,100,200 ng/g),用炭末推进实验的方法观察ghrelin对小鼠结肠推进的影响,研究阿托品、NG-硝基精氨酸甲酯和D-Lys3-GHRP-6(GHSR阻断剂)对ghrelin(100 ng/g)引起的小鼠结肠推进改变的影响.将小鼠近端结肠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,观察不同浓度的ghrelin(0.01、0.1、1和10 μmol/L)对肌条自发收缩幅度的影响.结果 ghrelin能显著提高小鼠的结肠推进速度,有明显的量效关系.阿托品、NG-硝基精氨酸甲酯、D-lys3-GHRP-6均能显著抑制ghrelin促进结肠推进的作用(t=10.230,12.560,11.590,P＜0.05).ghrelin能显著增加小鼠近端结肠环形平滑肌的自发收缩幅度,河豚毒素预处理肌条后ghrelin不能显著增加肌条的自发收缩幅度.结论 ghrelin可以显著增加小鼠结肠的推进,可能是通过结肠肌间神经丛的硝基能神经和胆碱能神经上的GHSR而起作用.

Effects of ghrelin on colonic motility in mice

Objective To investigate the effects of ghrelin on colonic motility in mice.Methods The eflfects of ghrelin on colonic propulsive movement were detected by charcoal suspension pushing test after injection of normal saline and different doses of ghrelin(20,50,100,200 ng/g).The effects of atropine,NG-nitro-L-arginine methylester hydrochloride(L-NAME)or D-Lys3-GHRP-6 on the changes of colonic propulsive movement caused by ghrelin(100 ng/g)were also investigated.In vitro,the effects of different doses of ghrelin(0.01,0.1,1,10μmol/L)on the spontaneous contraction amplitude of proximal colonic circular muscle strips were studied.Results Ghrelin significantly accelerated the colonic propulsive movement in dose-dependent manner,but the efiect was significantly inhibited in the presence of atropine,L-NAME or D-Lys3-GHRP-6(t=10.230,12.560,11.590,P＜0.05).Administration of ghrelin significantly increased the contraction amplitude of colonic circular muscle strips.but this effect was inhibited when the colonic circular muscle strips were pretreated by tetrodotoxin.ConclusionsGhrelin can accelerate colonic propulsive movement by activating growth hormone secretagogue receptor of cholinergic excitatory pathways and nitrergic nervous pathways in the enteric nervous system of colon.