Apelin-36通过中枢途径对大鼠摄食、胃肠运动调节作用的研究

Regulatory effect of Apelin-36 on food intake and gastrointestinal motility in rats via central pathway

目的探讨Apelin-36对大鼠摄食行为、胃肠运动的影响以及可能的途径。方法健康成年雄性SD大鼠共88只。采用随机数字表法从中随机选取32只大鼠,侧脑室埋管并注射生理盐水或Apelin-36(10 nmol/L)3μl、6μl、9μl,每组8只,测定48 h摄食量。采用随机数字表法选取16只大鼠侧脑室埋管并注射生理盐水或Apelin-36(10 nmol/L)9μl,每组8只,计算胃排空率。采用随机数字表法选取16只大鼠,麻醉后在十二指肠降部放置水囊,连接压力感受器,在体检测侧脑室注射生理盐水或Apelin-36后十二指肠运动变化情况,每组8只。随机数字表法选取16只大鼠,在体检测结肠的运动变化情况,每组8只。另外,随机数字表法选取8只大鼠,剖离胃体、十二指肠、结肠平滑肌条,离体条件下检测生理盐水或Apelin-36对平滑肌运动的影响。结果48 h累计单位体重摄食结果显示,Apelin-363μl、6μl、9μl组摄食量分别为(147.75±33.06)g/Kg、(127.69±23.94)g/Kg、(99.91±18.48)g/Kg,少于生理盐水组[(160.84±28.51)g/kg],并依次递减,差异有统计学意义(F=7.99,P<0.01),Apelin-369μl组摄食量较生理盐水组、Apelin-363μl组降低,均差异有统计学意义(t=6.49,5.10;均P<0.01);Apelin-369μl组黑夜(24 h)累计单位摄食量[(45.08±11.86)g/Kg],明显少于生理盐水组[(70.77±23.23)g/Kg](t=4.44,P<0.05)。侧脑室注射Apelin-36后大鼠胃排空率为(68.10±6.03)%,较生理盐水组[(79.21±7.94)%]降低,差异有统计学意义(t=3.15,P<0.01)。侧脑室注射Apelin-36后十二指肠降部平滑肌运动幅度降低至(0.29±0.08)g,明显低于生理盐水组[(0.81±0.16)g](t=8.36,P<0.01);而远端结肠的运动幅度[(0.20±0.09)g],较生理盐水组[(0.22±0.08)g]差异无统计学意义(t=0.31,P>0.05)。离体条件下Apelin-36对胃体[(0.19±0.06)g]、十二指肠[(0.09±0.02)g]、结肠平滑肌运动[(0.07±0.01)g]均无显著影响,与生理盐水组[(0.19±0.06)g、(0.08±0.01)g、(0.06±0.02)g]比较,均差异无统计学意义(t=0.13,0.22,0.41;均P>0.05)。结论侧脑室注射Apelin-36可减少摄食,抑制胃排空、十二指肠运动,但离体条件下Apelin-36对胃肠道平滑肌运动无直接影响。

Objective To investigate the effects of Apelin-36 on feeding behavior and gastrointestinal motility of rats and its possible pathway.Methods There were 88 healthy adult male SD rats in total.Thirty-two rats were randomly selected by random number table and got intracerebroventricular(ICV)injection with saline or Apelin-36(10 nmol/L)3μl,6μl and 9μl after lateral ventricular catheterization,with 8 rats in each group.The accumulative total of food intake per body weight for 48 hours were measured and calculated.Another 16 rats were randomly selected by random number table,and the gastric emptying rates were calculated in the 16 rats with lateral ventricle catheterization and injection of saline or Apelin-36(10 nmol/L)9μl,with 8 rats in each group.Sixteen rats were randomly selected by random number table and water sacs were placed in the descending duodenum and baroreceptors were connected.Duodenal motility changes were detected in vivo after lateral ventricular injection of saline or Apelin-36,with 8 rats in each group.Another 16 rats were randomly selected by random number table and colon motility changes were measured in vivo by the same method,with 8 rats in each group.In addition,smooth muscle strips of stomach,duodenum and colon from 8 rats randomly selected by random number table who were dissected to detect the effects of saline or Apelin-36 on the smooth muscle movement in vitro.Results The accumulative food intake/body weight of Apelin-363μl,6μl and 9μl were(147.75±33.06)g/Kg,(127.69±23.94)g/Kg,(99.91±18.48)g/Kg respectively,less than that of saline injected group[(160.84±28.51)g/kg](F=7.99,P<0.01).Compared with saline and Apelin-363μl group,the food intake of Apelin-369μl group was significantly lower(t=6.49,5.10,all P<0.01).The accumulative food intake/body weight at night of Apelin-369μl group was(45.08±11.86)g/Kg,significantly less than that of saline injected group[(70.77±23.23)g/Kg](t=4.44,P<0.05).The gastric emptying rate of rats injected with Apelin-36 was(68.10±6.03)%,which was significantly lower than that of saline injected group[(79.21±7.94)%](t=3.15,P<0.01).After ICV injection of Apelin-36,the motive amplitude of descending duodenum decreased to(0.29±0.08)g,significantly lower than that of saline injected group[(0.81±0.16)g](t=8.36,P<0.01).While there was no significant difference of the motive amplitude of distal colon between Apelin-36 and saline injected group[(t=0.31,P>0.05)].Apelin-36 showed no significant effects on gastric[(0.19±0.06)g],duodenal[(0.09±0.02)g]and colonic[(0.07±0.01)g]smooth muscle movement in vitro compared with saline[(0.19±0.06)g,(0.08±0.01)g,(0.06±0.02)g](t=0.13,0.22,0.41,all P>0.05).Conclusion Intracerebroventricular injection of Apelin-36 could reduce food intake,inhibit gastric emptying and duodenal motility,while Apelin-36 shows no direct effect on gastrointestinal smooth muscle movement in vitro.