侧脑室注射apelin-13对大鼠远端结肠推进的影响及机制研究

Effect of intracerebroventricular administration of apelin-13 on the distal colonic transit in rats and its mechanism

目的探讨侧脑室apelin-13对大鼠远端结肠推进活动的影响及其作用机制。方法将SD大鼠随机分为6组,每组8只,生理盐水为对照组(i.c.v.,2μL)、apelin-13组(0.1、0.3、1、3、10 nmol,i.c.v.,2μL),通过排珠实验检测各个剂量的apelin-13对大鼠远端结肠推进活动的影响;对照组(3组)分别为大鼠腹腔1次性注射2 m L的M型胆碱能受体的阻断剂阿托品(atropine,ATR)(20mg/kg)组、肾上腺素受体阻断剂酚妥拉明(phentolamine,PHE)(1 mg/kg)和普洛奈尔(propranolol,PRO)(1 mg/kg)组、N型胆碱能受体的阻断剂六烃季铵(hexamethonium,HEX)(1 mg/kg)组;20 min后在对照组基础上,各组分别侧脑室注射2μL 1 nmol apelin-13,考察apelin-13在结肠推进作用上的可能机制。结果与对照组相比,apelin-13以剂量依赖的方式延长了实验动物的排珠时间(P<0.01),即抑制大鼠远端结肠的推进活动;N型胆碱能受体的阻断剂HEX能完全消除apelin-13对结肠推进的抑制作用;而M型胆碱能受体的阻断剂ATR以及肾上腺素受体阻断剂PHE和PRO都不能影响apelin-13在结肠推进上的作用。结论中枢apelin-13能剂量依赖的抑制大鼠远端结肠的推进,它的这种作用可能是通过N型胆碱能受体实现的。

Objective To discuss the effect and mechanism of intracerebroventricular（ i. c. v.） administration of apelin-13 on the distal colonic transit in rats. Methods SD rats were randomly divided into 6 groups,8 rats for each group. Saline group as control group（ i. c. v.,2 μL）; apelin-13 group（ 0. 1,0. 3,1,3,10 nmol,i. c. v.,2 μL）,the effects of intracerebroventricular administration of apelin-13（ 0. 1-10 nmol） once time on the distal colonic transit in rats detected by the bead expulsion experiments; the control group（ 3 group） was respectively intraperitoneal injection of N-cholinergic receptor antagonist Hexamethonium（ Hex） group,M-cholinergic receptor antagonist Atropine（ ATR） group,the adrenergic receptor antagonist Phentolamine（ PHE）and Propranolol（ PRO） group,20 min later,on the basis of control group,rats in each group were intracerebroventricular injected 2 μL 1 nmol apelin-13,studied the possible mechanism of apelin-13 on the distal colonic transit in rats. Results Compared with the control group,apelin-13 dose dependently prolonged bead expulsion time（ P〈0. 01） and N-cholinergic receptor antagonist HEX could completely eliminate the inhibitory effect of apelin-13 on colonic propulsion; M-cholinergic receptor blocker ATR and adrenergic receptor antagonists PHE and PRO could not affect the effects of apelin-13 on the colonic transit in rats. Conclusion Apelin-13 can dose dependently inhibit rat distal colonic transit,which may be through the N-cholinergic receptor pathway.