摘要
目的探讨生长激素促分泌素受体(GHS-R)内源性激动剂ghrelin及其合成肽生长激素释放肽6(GHRP.6)对小鼠胃动力影响及机制。方法小鼠随机分组后,分别注射生理盐水、ghrelin(20、50、100和200μg/kg)及GHRP-6(20、50、100和200μg/kg),用灌食酚红的方法研究ghrelin和GHRP-6对小鼠胃排空的影响,并研究阿托品、一氧化氮合成酶抑制剂左旋.硝基精氨酸甲基酯(L-NAME)和GHS.R阻断剂D.lys3-GHRP-6对ghrelin和GHRP-6引起小鼠胃排空改变的影响。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,观察不同浓度的ghrelin(0.01、0.1.0和10.0μmol/L)和GHRP-6(0.01、0.1、1.0和10.0μmol/L)对肌条自发收缩活动的影响。结果GHRP-6和ghrelin注射剂量在50、100和200μg/kg时,均能显著提高小鼠的胃排空(P〈0.05)。阿托品、L-NAME和D-lys3-GHRP-6均能显著抑制GHRP-6或ghrelin促进胃排空的作用(P〈0.05)。GHRP-6和ghrelin浓度在0.1、1.0和10.0μmol/L时,均能显著增加小鼠胃底环形平滑肌条的自发收缩幅度(P〈0.05);在河豚毒素同时存在的情况下,GHRP-6或ghrelin均不能显著增加肌条的自发收缩幅度(P〉0.05)。结论GHRP-6和ghrelin均可显著增加小鼠的胃排空.其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。
Objective To investigate the effect and mechanism of ghrelin and its synthetic peptide GHRP-6 on gastric motor in mice. Methods In vivo, the dose-dependent effects of ghrelin (20,50,100,200 μg/kg) and GHRP-6 (20,50,100,200 μg/kg) on gastric emptying were measured by intragastric application of phenol red test which was adapted for use in mice. The effects of atropine, NG-nitro-L-arginine methyl ester (L-NAME), and D-Lys3-GHRP-6 (GHS-R antagonist) on the gastric motor induced by ghrelin and GHRP-6 (100 μg/kg) were also investigated. In vitro, the effects of ghrelin (0.01,0.1,1.0,10.0 μmol/L) and GHRP-6 (0.01,0.1,1.0,10.0 μmol/L) on spontaneous contraction of mice fundic muscle strips were studied as well. Results Both ghrelin (50, 100,200 μg/kg) and GHRP-6 (50,100,200 μg/kg) significantly accelerated gastric emptying (P〈 0.05), but they failed to accelerate gastric emptying in the presence of atropine, L-NAME and D- Lys3-GHRP-6 (P〈0.05). Ghrelin (0.1, 1.0, 10.0 μmol/L) and GHRP-6 (0.1, 1.0, 10.0 μmol/L) induced significant contraction of fundic muscle strips in concentration-dependent manner (P〈0.05), which could be blocked by tetredotoxin. Conclusion Ghrelin and its synthetic peptide GHRP-6 accelerate gastric emptying perhaps by activating GHS-R of cholinergic excitatory pathways and nitrergic nervous pathways in the enteric nervous system.
出处
《中华胃肠外科杂志》
CAS
2008年第2期172-176,共5页
Chinese Journal of Gastrointestinal Surgery
基金
国家自然科学基金(30400429)