本文主要研究内容
作者张顺（2019）在《“下丘脑—脑干—肠脑轴”中CRF在大鼠束缚—浸水应激中的作用》一文中研究指出：束缚-浸水应激模型（Restraint Water-Immersion Stress,RWIS）是一种快速对大鼠心理和生理造成伤害的刺激模型。在这种应激模型中,大鼠在短时间内因受到刺激,体温下降,胃肠功能紊乱,导致胃酸分泌增加和急性胃黏膜损伤。肠神经系统是位于胃肠道壁中的神经元、神经递质和肠细胞组成的网络,控制和调节胃肠道中的平滑肌,黏膜上皮和血管效应系统,它的调节具有高度的自主性,因此也被称为“肠脑”。经本实验室的早期研究发现,大鼠在一定的应激时间段内,随着束缚-浸水的时间增长,下丘脑的室旁核（hypothalamic paraventricular nucleus,PVN）、视上核（supraoptic nucleus,SON）、孤束核（Solitary Nucleus,NTS）、迷走神经背核（dorsal motor nucleus of the vagus,DMV）和肠道肌间神经丛中Fos和GFAP（Glial Fibrillary Acidic Protein,GFAP）的表达水平显著升高,我们推测束缚-浸水应激造成胃黏膜损伤不只是涉及到脑干内神经元的过度活动这种初级中枢机制[75],所以我们提出了“下丘脑-脑干-肠脑轴”环路参与了对应激的调控。而促肾上腺皮质激素释放激素（Corticotropin-Releasing Factor,CRF）作为下丘脑的室旁核、视上核释放的非常重要的激素之一,已研究表明其参与了多种应激（热刺激、冷刺激、感染和毒物刺激）反应,但促肾上腺皮质激素释放激素（CRF）及其受体是否参与了束缚-浸水应激尚未见报道。因此,我们提出以下几个问题:1.CRF及其受体是否介导和参与了RWIS过程,并在RWIS中各时间段有何变化?2.侧脑室注射CRF受体阻断剂Astressin和CRF后,对孤束核及肠道内的神经元和胶质细胞有何影响?3.CRF若参与束缚-浸水的过程,是通过哪条信号路径起作用?为了解决上述问题,我们实验设计如下:实验研究一:大鼠随机分为对照组（RWIS 0h）和应激组（RWIS 1h,RWIS 2h,RWIS3h）后,采用免疫组化和免疫印迹法检测大鼠CRF及其受体表达的影响,以探讨CRF及其受体是否参与了RWIS过程。实验研究二:将大鼠分为对照组（侧脑室注射生理盐水）、CRF组（侧脑室注射CRF）和Astressin组（侧脑室注射CRF-R抑制剂Astressin）,大鼠束缚-浸水应激1h后,免疫组化和免疫印迹法检测NTS、DMV以及肠神经系统中Fos、GFAP、p-ERK1/2、NOS表达,探讨CRF在束缚浸水过程中的作用?实验研究三:将大鼠分为对照组（侧脑室注射生理盐水）、CRF组（侧脑室注射CRF）和PD98059+CRF组（侧脑室注射p-ERK1/2特异性抑制剂PD98059和CRF）,大鼠束缚-浸水应激1h后,免疫组化和免疫印迹法检测NTS和DMV内Fos和星形胶质细胞的标记物GFAP表达的变化,探究CRF参与束缚-浸水的信号途径?实验研究四:将大鼠分为对照组（侧脑室注射生理盐水）、CRF组和Astressin组,大鼠束缚-浸水应激1h后,免疫组化和免疫印迹法检测肠神经系统中的Claudin-1、Occludin和胃黏膜中的MUC5AC表达变化,探究CRF对胃肠道功能的影响?实验结果:1.与对照组相比,实验组大鼠脑干迷走复合体内CRF-R1与肠神经系统内CRF的表达明显增加,且呈时间依赖性,在3h达到了最高。而与对照组相比,实验组大鼠迷走复合体内CRF-R2的表达明显降低,且呈时间依赖性,在3h达到了最低。表明肠神经系统内CRF及脑干（NTS、DMV）内CRF-R1被激活,参与了RWIS过程。2.与侧脑室注射生理盐水对照组相比,侧脑室注射CRF-R抑制剂Astressin,束缚-浸水应激1h后,实验组NTS、DMV以及肠神经系统中的Fos表达、星形胶质细胞GFAP、p-ERK1/2、NOS表达都显著降低。而侧脑室注射CRF,束缚-浸水应激1h后,实验组NTS、DMV以及肠神经系统中的Fos表达、星形胶质细胞GFAP、p-ERK1/2、NOS表达都显著升高,表明促肾上腺激素释放激素可能激活了脑干和肠神经系统内一氧化氮能神经元参与了在束缚-浸水应激过程。3.与侧脑室注射CRF对照组相比,侧脑室注射p-ERK1/2特异性抑制剂PD98059和CRF后,实验组NTS、DMV以及肠神经系统中的Fos和星形胶质细胞的标记物GFAP表达明显下降,表明CRF可能通过ERK1/2信号通路参与束缚-浸水过程。4.与侧脑室注射生理盐水对照组相比,侧脑室注射CRF组肠神经系统中的Claudin-1、Occludin和胃黏膜中的MUC5AC表达显著降低。表明束缚-浸水对大鼠造成胃机能的损伤和机体内部发生了紊乱,而CRF在这个过程中可能加速了炎症反应和胃溃疡,而且这个过程主要是通过ERK1/2信号通路进行调控的。实验结论如下:1、脑干内的CRF受体CRF-R和结肠内的CRF都参与了束缚浸水应激的过程。2、CRF主要是通过ERK1/2信号通路对束缚浸水后造成的胃肠机能紊乱进行调控的。
Abstract
shu fu -jin shui ying ji mo xing （Restraint Water-Immersion Stress,RWIS）shi yi chong kuai su dui da shu xin li he sheng li zao cheng shang hai de ci ji mo xing 。zai zhe chong ying ji mo xing zhong ,da shu zai duan shi jian nei yin shou dao ci ji ,ti wen xia jiang ,wei chang gong neng wen luan ,dao zhi wei suan fen bi zeng jia he ji xing wei nian mo sun shang 。chang shen jing ji tong shi wei yu wei chang dao bi zhong de shen jing yuan 、shen jing di zhi he chang xi bao zu cheng de wang lao ,kong zhi he diao jie wei chang dao zhong de ping hua ji ,nian mo shang pi he xie guan xiao ying ji tong ,ta de diao jie ju you gao du de zi zhu xing ,yin ci ye bei chen wei “chang nao ”。jing ben shi yan shi de zao ji yan jiu fa xian ,da shu zai yi ding de ying ji shi jian duan nei ,sui zhao shu fu -jin shui de shi jian zeng chang ,xia qiu nao de shi pang he （hypothalamic paraventricular nucleus,PVN）、shi shang he （supraoptic nucleus,SON）、gu shu he （Solitary Nucleus,NTS）、mi zou shen jing bei he （dorsal motor nucleus of the vagus,DMV）he chang dao ji jian shen jing cong zhong Foshe GFAP（Glial Fibrillary Acidic Protein,GFAP）de biao da shui ping xian zhe sheng gao ,wo men tui ce shu fu -jin shui ying ji zao cheng wei nian mo sun shang bu zhi shi she ji dao nao gan nei shen jing yuan de guo du huo dong zhe chong chu ji zhong shu ji zhi [75],suo yi wo men di chu le “xia qiu nao -nao gan -chang nao zhou ”huan lu can yu le dui ying ji de diao kong 。er cu shen shang xian pi zhi ji su shi fang ji su （Corticotropin-Releasing Factor,CRF）zuo wei xia qiu nao de shi pang he 、shi shang he shi fang de fei chang chong yao de ji su zhi yi ,yi yan jiu biao ming ji can yu le duo chong ying ji （re ci ji 、leng ci ji 、gan ran he du wu ci ji ）fan ying ,dan cu shen shang xian pi zhi ji su shi fang ji su （CRF）ji ji shou ti shi fou can yu le shu fu -jin shui ying ji shang wei jian bao dao 。yin ci ,wo men di chu yi xia ji ge wen ti :1.CRFji ji shou ti shi fou jie dao he can yu le RWISguo cheng ,bing zai RWISzhong ge shi jian duan you he bian hua ?2.ce nao shi zhu she CRFshou ti zu duan ji Astressinhe CRFhou ,dui gu shu he ji chang dao nei de shen jing yuan he jiao zhi xi bao you he ying xiang ?3.CRFre can yu shu fu -jin shui de guo cheng ,shi tong guo na tiao xin hao lu jing qi zuo yong ?wei le jie jue shang shu wen ti ,wo men shi yan she ji ru xia :shi yan yan jiu yi :da shu sui ji fen wei dui zhao zu （RWIS 0h）he ying ji zu （RWIS 1h,RWIS 2h,RWIS3h）hou ,cai yong mian yi zu hua he mian yi yin ji fa jian ce da shu CRFji ji shou ti biao da de ying xiang ,yi tan tao CRFji ji shou ti shi fou can yu le RWISguo cheng 。shi yan yan jiu er :jiang da shu fen wei dui zhao zu （ce nao shi zhu she sheng li yan shui ）、CRFzu （ce nao shi zhu she CRF）he Astressinzu （ce nao shi zhu she CRF-Ryi zhi ji Astressin）,da shu shu fu -jin shui ying ji 1hhou ,mian yi zu hua he mian yi yin ji fa jian ce NTS、DMVyi ji chang shen jing ji tong zhong Fos、GFAP、p-ERK1/2、NOSbiao da ,tan tao CRFzai shu fu jin shui guo cheng zhong de zuo yong ?shi yan yan jiu san :jiang da shu fen wei dui zhao zu （ce nao shi zhu she sheng li yan shui ）、CRFzu （ce nao shi zhu she CRF）he PD98059+CRFzu （ce nao shi zhu she p-ERK1/2te yi xing yi zhi ji PD98059he CRF）,da shu shu fu -jin shui ying ji 1hhou ,mian yi zu hua he mian yi yin ji fa jian ce NTShe DMVnei Foshe xing xing jiao zhi xi bao de biao ji wu GFAPbiao da de bian hua ,tan jiu CRFcan yu shu fu -jin shui de xin hao tu jing ?shi yan yan jiu si :jiang da shu fen wei dui zhao zu （ce nao shi zhu she sheng li yan shui ）、CRFzu he Astressinzu ,da shu shu fu -jin shui ying ji 1hhou ,mian yi zu hua he mian yi yin ji fa jian ce chang shen jing ji tong zhong de Claudin-1、Occludinhe wei nian mo zhong de MUC5ACbiao da bian hua ,tan jiu CRFdui wei chang dao gong neng de ying xiang ?shi yan jie guo :1.yu dui zhao zu xiang bi ,shi yan zu da shu nao gan mi zou fu ge ti nei CRF-R1yu chang shen jing ji tong nei CRFde biao da ming xian zeng jia ,ju cheng shi jian yi lai xing ,zai 3hda dao le zui gao 。er yu dui zhao zu xiang bi ,shi yan zu da shu mi zou fu ge ti nei CRF-R2de biao da ming xian jiang di ,ju cheng shi jian yi lai xing ,zai 3hda dao le zui di 。biao ming chang shen jing ji tong nei CRFji nao gan （NTS、DMV）nei CRF-R1bei ji huo ,can yu le RWISguo cheng 。2.yu ce nao shi zhu she sheng li yan shui dui zhao zu xiang bi ,ce nao shi zhu she CRF-Ryi zhi ji Astressin,shu fu -jin shui ying ji 1hhou ,shi yan zu NTS、DMVyi ji chang shen jing ji tong zhong de Fosbiao da 、xing xing jiao zhi xi bao GFAP、p-ERK1/2、NOSbiao da dou xian zhe jiang di 。er ce nao shi zhu she CRF,shu fu -jin shui ying ji 1hhou ,shi yan zu NTS、DMVyi ji chang shen jing ji tong zhong de Fosbiao da 、xing xing jiao zhi xi bao GFAP、p-ERK1/2、NOSbiao da dou xian zhe sheng gao ,biao ming cu shen shang xian ji su shi fang ji su ke neng ji huo le nao gan he chang shen jing ji tong nei yi yang hua dan neng shen jing yuan can yu le zai shu fu -jin shui ying ji guo cheng 。3.yu ce nao shi zhu she CRFdui zhao zu xiang bi ,ce nao shi zhu she p-ERK1/2te yi xing yi zhi ji PD98059he CRFhou ,shi yan zu NTS、DMVyi ji chang shen jing ji tong zhong de Foshe xing xing jiao zhi xi bao de biao ji wu GFAPbiao da ming xian xia jiang ,biao ming CRFke neng tong guo ERK1/2xin hao tong lu can yu shu fu -jin shui guo cheng 。4.yu ce nao shi zhu she sheng li yan shui dui zhao zu xiang bi ,ce nao shi zhu she CRFzu chang shen jing ji tong zhong de Claudin-1、Occludinhe wei nian mo zhong de MUC5ACbiao da xian zhe jiang di 。biao ming shu fu -jin shui dui da shu zao cheng wei ji neng de sun shang he ji ti nei bu fa sheng le wen luan ,er CRFzai zhe ge guo cheng zhong ke neng jia su le yan zheng fan ying he wei hui yang ,er ju zhe ge guo cheng zhu yao shi tong guo ERK1/2xin hao tong lu jin hang diao kong de 。shi yan jie lun ru xia :1、nao gan nei de CRFshou ti CRF-Rhe jie chang nei de CRFdou can yu le shu fu jin shui ying ji de guo cheng 。2、CRFzhu yao shi tong guo ERK1/2xin hao tong lu dui shu fu jin shui hou zao cheng de wei chang ji neng wen luan jin hang diao kong de 。
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论文作者分别是来自山东师范大学的张顺，发表于刊物山东师范大学2019-07-06论文，是一篇关于下丘脑脑干肠脑轴论文,肠神经系统论文,信号通路论文,山东师范大学2019-07-06论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自山东师范大学2019-07-06论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。