本文主要研究内容
作者贾丽(2019)在《HSPD1胞内介导猪链球菌2型烯醇化酶诱导脑微血管内皮细胞凋亡的机制》一文中研究指出:猪链球菌2型(Streptococcus suis Type 2,SS2)是诱发细菌性脑膜炎的一种重要病原菌,烯醇化酶(Enolase,ENO)是SS2感染诱发脑膜炎过程中的重要毒力分子。本课题组前期发现猪链球菌2型烯醇化酶(SS2-ENO)诱导脑微血管内皮细胞(BMEC)凋亡过程中,细胞热休克蛋白60(HSPD1)含量显著升高,但其具体作用尚不明确。因此,本研究针对HSPD1介导SS2-ENO诱导脑微血管内皮细胞凋亡机制展开以下研究。为探讨HSPD1在ENO诱导BMEC凋亡中的作用,本研究通过Western blot、等方法,分析HSPD1含量对BMEC凋亡的影响。研究结果表明:ENO诱导细胞凋亡过程中,胞内和胞外HSPD1含量升高。且胞内过表达HSPD1和胞外添加HSPD1可促进ENO诱导的细胞凋亡;胞内敲低HSPD1和胞外抗体阻断HSPD1,会抑制该凋亡。证明HSPD1可促进ENO诱导的细胞凋亡。为研究HSPD1在ENO诱导细胞凋亡过程中的定位,本研究通过荧光标记等方法进行分析。结果显示,在ENO诱导细胞凋亡过程中,线粒体HSPD1含量逐渐减少,胞浆HSPD1含量逐渐增多,HSPD1逐渐由线粒体向胞浆转移。线粒体渗透性也随之改变。说明ENO诱导细胞凋亡过程中,线粒体膜渗透性增大,致使HSPD1由线粒体向胞浆、进而向胞外发生转移。进一步对胞内胞外HSPD1介导细胞凋亡的分子机制进行研究。通过Co-IP、免疫荧光染色等方法验证胞内HSPD1的互作蛋白并分析其参与的信号通路,发现胞内HSPD1的互作蛋白为actin,并通过Smac-XIAP-Caspase 3信号通路介导凋亡发生。TLR4介导了胞外HSPD1诱导细胞凋亡的过程。最后为验证HSPD1对血脑屏障(BBB)通透性的影响,以体外BBB共培养模型和健康小鼠进行实验。结果显示体外模型添加HSPD1或小鼠尾静脉注射HSPD1后,体外BBB模型的TEER值显著降低,小鼠体内脑组织摄入的伊蓝染料浓度升高,证实HSPD1可以增加BBB的通透性。本研究证实,ENO诱导的脑微血管内皮细胞凋亡,可使胞内胞外HSPD1含量升高,并由线粒体向胞浆、胞外转移,增加血脑屏障的通透性。该研究阐明了HSPD1对细胞凋亡的作用及其对BBB通透性的影响,丰富了人们对HSPD1功能上的认识,也为SS2脑膜炎致病机制的研究提供重要的理论基础。
Abstract
zhu lian qiu jun 2xing (Streptococcus suis Type 2,SS2)shi you fa xi jun xing nao mo yan de yi chong chong yao bing yuan jun ,xi chun hua mei (Enolase,ENO)shi SS2gan ran you fa nao mo yan guo cheng zhong de chong yao du li fen zi 。ben ke ti zu qian ji fa xian zhu lian qiu jun 2xing xi chun hua mei (SS2-ENO)you dao nao wei xie guan nei pi xi bao (BMEC)diao wang guo cheng zhong ,xi bao re xiu ke dan bai 60(HSPD1)han liang xian zhe sheng gao ,dan ji ju ti zuo yong shang bu ming que 。yin ci ,ben yan jiu zhen dui HSPD1jie dao SS2-ENOyou dao nao wei xie guan nei pi xi bao diao wang ji zhi zhan kai yi xia yan jiu 。wei tan tao HSPD1zai ENOyou dao BMECdiao wang zhong de zuo yong ,ben yan jiu tong guo Western blot、deng fang fa ,fen xi HSPD1han liang dui BMECdiao wang de ying xiang 。yan jiu jie guo biao ming :ENOyou dao xi bao diao wang guo cheng zhong ,bao nei he bao wai HSPD1han liang sheng gao 。ju bao nei guo biao da HSPD1he bao wai tian jia HSPD1ke cu jin ENOyou dao de xi bao diao wang ;bao nei qiao di HSPD1he bao wai kang ti zu duan HSPD1,hui yi zhi gai diao wang 。zheng ming HSPD1ke cu jin ENOyou dao de xi bao diao wang 。wei yan jiu HSPD1zai ENOyou dao xi bao diao wang guo cheng zhong de ding wei ,ben yan jiu tong guo ying guang biao ji deng fang fa jin hang fen xi 。jie guo xian shi ,zai ENOyou dao xi bao diao wang guo cheng zhong ,xian li ti HSPD1han liang zhu jian jian shao ,bao jiang HSPD1han liang zhu jian zeng duo ,HSPD1zhu jian you xian li ti xiang bao jiang zhuai yi 。xian li ti shen tou xing ye sui zhi gai bian 。shui ming ENOyou dao xi bao diao wang guo cheng zhong ,xian li ti mo shen tou xing zeng da ,zhi shi HSPD1you xian li ti xiang bao jiang 、jin er xiang bao wai fa sheng zhuai yi 。jin yi bu dui bao nei bao wai HSPD1jie dao xi bao diao wang de fen zi ji zhi jin hang yan jiu 。tong guo Co-IP、mian yi ying guang ran se deng fang fa yan zheng bao nei HSPD1de hu zuo dan bai bing fen xi ji can yu de xin hao tong lu ,fa xian bao nei HSPD1de hu zuo dan bai wei actin,bing tong guo Smac-XIAP-Caspase 3xin hao tong lu jie dao diao wang fa sheng 。TLR4jie dao le bao wai HSPD1you dao xi bao diao wang de guo cheng 。zui hou wei yan zheng HSPD1dui xie nao bing zhang (BBB)tong tou xing de ying xiang ,yi ti wai BBBgong pei yang mo xing he jian kang xiao shu jin hang shi yan 。jie guo xian shi ti wai mo xing tian jia HSPD1huo xiao shu wei jing mai zhu she HSPD1hou ,ti wai BBBmo xing de TEERzhi xian zhe jiang di ,xiao shu ti nei nao zu zhi she ru de yi lan ran liao nong du sheng gao ,zheng shi HSPD1ke yi zeng jia BBBde tong tou xing 。ben yan jiu zheng shi ,ENOyou dao de nao wei xie guan nei pi xi bao diao wang ,ke shi bao nei bao wai HSPD1han liang sheng gao ,bing you xian li ti xiang bao jiang 、bao wai zhuai yi ,zeng jia xie nao bing zhang de tong tou xing 。gai yan jiu chan ming le HSPD1dui xi bao diao wang de zuo yong ji ji dui BBBtong tou xing de ying xiang ,feng fu le ren men dui HSPD1gong neng shang de ren shi ,ye wei SS2nao mo yan zhi bing ji zhi de yan jiu di gong chong yao de li lun ji chu 。
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论文作者分别是来自吉林大学的贾丽,发表于刊物吉林大学2019-06-25论文,是一篇关于猪链球菌型论文,脑膜炎论文,细胞凋亡论文,血脑屏障论文,吉林大学2019-06-25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,资料来自吉林大学2019-06-25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。
标签:猪链球菌型论文; 脑膜炎论文; 细胞凋亡论文; 血脑屏障论文; 吉林大学2019-06-25论文;