Ghrelin对大鼠小肠转运的作用及对中枢和胃肠道c-Fos表达的影响  

Effects of ghrelin on small intestinal transit and c-Fos expression in the central and digestive tracts in rats

作　　者：王燕[1] 史海涛[1] 秦斌[1] 姜炅[1] 赵菊辉[1] 赵红莉[1] 

机构地区：[1]西安交通大学医学院第二附属医院消化内科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2014年第5期611-617,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81100258)~~

摘　　要：目的观察静脉注射ghrelin对大鼠小肠转运的作用及对中枢和胃肠道c-Fos表达的影响。方法大鼠禁食24h,静脉注射ghrelin(2、5、10、20μg/kg),经预先埋置在十二指肠内的导管注入伊文氏蓝溶液,观察不同剂量ghrelin对大鼠小肠转运的影响及ghrelin受体拮抗剂(D-Lys3)GHRP-6对其作用的影响。采用免疫组织化学和图像分析方法观察静脉给予ghrelin对大鼠中枢和胃肠道的c-Fos蛋白的激活情况;观察(D-Lys3)GHRP-6对ghrelin作用的影响。结果 1静脉给予ghrelin 2μg/kg对大鼠小肠转运无显著影响,给予ghrelin 5、10、20μg/kg可剂量依赖性促进小肠转运,此作用可被(D-Lys3)GHRP-6阻断。2静脉注射ghrelin可激活中枢多个部位的c-Fos表达,包括下丘脑室旁核、弓状核、杏仁内侧核、迷走神经背核、孤束核、延髓最后区和胸腰段脊髓背角c-Fos均有表达;胃、十二指肠、空肠和近端结肠肠神经丛的c-Fos有不同程度的表达,其中以胃和近端结肠的c-Fos表达最为显著。应用ghrelin受体拮抗剂(D-Lys3)GHRP-6可抑制ghrelin激活的c-Fos表达。结论 Ghrelin可促进小肠转运,其促动力作用由其受体GHS-R所介导;静脉给予ghrelin可通过肠神经系统和中枢神经系统调节小肠运动。Objective To investigate the effects and mechanism of ghrelin injected intravenously on small intestinal transit and c-Fos expression in the central nervous system （CNS） and the enteric nervous system （ENS）.Methods Rats were supplied with an intraduodenal catheter.After fasted for 24 h,rats received intravenous injection of ghrelin （2,5,10 or 20 μg/kg） respectively.The small intestinal transit was measured after instillation of Evans blue through the intraduodenal catheter.Another group of rats were pretreated with ghrelin receptor antagonist （D-Lys3） GHRP-6 10 min before ghrelin administration.The c-Fos activation on the CNS and ENS through intravenous injection of ghrelin was studied by the immunohistochemistry and imaging analysis.Results ① Ghrelin 2 μg/kg had little influence on small intestinal transit; however,ghrelin 5,10 or 20 μg/kg enhanced small intestinal transit dose-dependently.This effect was inhibited by its receptor antagonist.（②） In the CNS,the c-Fos expression of several nuclei such as the arcuate nucleus and paraventricular nucleus was increased by intravenous injection of ghrelin.And the c-Fos expression in the duodenum,jejunum,and proximate colon was also activated by ghrelin.The receptor antagonist inhibited the effects of ghrelin.Conclusion Ghrelin appears to be closely related to small intestinal motility.Its receptor GHS-R regulates its activity.Intravenous administration of ghrelin can regulate the intestinal motility through the ENS and CNS.

关 键 词：GHRELIN 小肠转运 生长激素促分泌素受体 胃肠动力 C-FOS 

分 类 号：R333.3[医药卫生—人体生理学]