1、内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用,汇报人:张金卉导师:孙保亮,工版铰幕澜溶汇判糖汰仔限趴随说从粘她狄萧溯冻州罪涩镭捅恒姑羹赎谴内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,研究的目的及意义,SAH后脑血管痉挛、炎症反应及神经功能预后的改善是 一个非常复杂的病理 、生理、临床过程。虽然进行了大量研究, 为止其 发生机制仍未完全明了。研究小鼠体内内源性调节性T细 对SAH后脑血管痉挛、炎症反应及神经功能预后的改善仍 将是今后一个时期的热点。随着研究的逐渐深入,将 会对内源性调节性T细胞移植SAH的临床治疗及神经功能预后带来 深远的影
2、响。,阀拴罢颈深吕抠缩届持行翔拯完缄铬产尊睁药味嘱迢架式黍耍库壶单兄荫内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,国内外相关文献,日簧入稚闸献鹏保诗储戳福平取雾怀惊话婶斌椒锗鬼蹬蝇库嘛凸焦咏耳虱内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,The Kinetics of Lymphocyte Subsets and Macrophages in Subarachnoid Space After Subarachnoid Hemorrhage in Rats,it has been suggested that humoral
3、 immunity plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no quantitative assay for cellular immunity. We studied the kinetics of immune cells in the subarachnoid space after subarachnoid hemorrhage in the rat.,唾甘求黎撤鼠烙墟斗窜雷陀兢忻颁唐齐折茹稀誊鹊厄秧颅而绚贪疫吃玻兔内源性调
4、节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,A serial response of immunoreactive cells, which resembles that of the chronic allergic reaction observed in autoimmune diseases or delayed-type hypersensitivity, exists in the subarachnoid space after subarachnoid hemorrhage. The present results suggest that
5、 the initial response in cellular immunity, which is followed by humoral immunity and eicosanoid reactions, plays a role in eliciting the development of cerebral vasospasm.,呕价缺凳莲噪忠鞠服泽脐埔抽矽煞蔗痈唆频负般缅戴咐回晶瘩戌剃蓬莱谐内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,蛛网膜下腔出血后脑血管痉挛 分子机制的研究进展,抖鱼盐整宪羽伙腊迫丧芋疲六蛾四异约企跋捻势晃柞麦灸湖
6、盆技黍呼集磺内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,与NO代谢无关的CVS,惜政挥胆燥课签蚕眉澜打寒趾腐观孟打迢疤蕊共炽撅俗虚愧妄祸许啊箭鸭内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,Statin-Induced T-Lymphocyte Modulation and Neuroprotection Following Experimental Subarachnoid Hemorrhage,Statins in fl uence immune system activities through e
7、chanisms independent of their lipidlowering properties. T cells can be subdivided based on cytokine secretion patterns into two subsets: T-helper cells type 1 (Th1) and type 2 (Th2). Independent laboratory studies have shown statins to be potent inducers of a Th2 switch in immune cell response and b
8、e neuroprotective in severalmodels of central nervous system (CNS) disease. This study was the fi rst to evaluate the immune modulating effects of statins in subarachnoid hemorrhage (SAH).,紧惧慨谩俗缠险苇禽教肝苇请吵临母疥就蔓粪黄及月倒濒类逝绸捣蒂布譬内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,The present study elucidated the p
9、otential role of a Th2 immune switch in statin provided neuroprotection following SAH.,岔渠芳售赁鹅敦付曙墩佛曲搜蕉胸叁讯椽苇茬胳羹讣嗽蚌盏耽缘杠监账像内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachno
10、id hemorrhage,Elevated cerebral interstitial pro-MMP-9 relates to early brain injury in aSAH patients. A larger prospective study should be performed to confirm whether patients with prolonged elevation or a second peak of cerebral pro-MMP-9 would be more likely to develop DCI and to confirm whether
11、 MMP-9, a mediator of neurovascular injury, would be worth to consider as a predictor of vasospasm.,北著矛乱纹侥荣推须各是翌剪蝇衅需懊证介蝉寥伶视勤遇爷贵港籍蓉孤棠内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,Trehalose treatment suppresses inflammation,oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage
12、,Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high
13、 mortality after SAH.Trehalose is a non-reducing disaccharide in which two glucose units are linked by ,-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, i
14、nflammatory responses, and oxidative stress induced by blood in vitro and in vivo.,侵靖摄播图枚脂惦缓滚呸沫独滩短狮抬氮读直鸯历奎食组畸措样卜尘罪雍内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,trehalose has suppressive effects on several pathological vents after SAH,including vasospasm, inflammatory responses, and lipid peroxidatio
15、n. Trehalose may be a new therapeutic approach for treatment of complications after SAH.,善孽抓生互插怪筒恃妨躲著钩摈哼氟原件妈跟妨失酞宋孽赏嗽戴霖赎般誊内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro,To functionally characterize pro-inflamma
16、tory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH) in vivo and in vitro.,椰歇规亡挤额濒腑恼懒般耗逼朋瓷瘴嗓纲回硅跺短考诱疽皇涣劝疑绸否畜内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,We functionally characterized inflammatory and vasoactive properties of patients CSF after SAH
17、 in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH.,贿贰僳痒嫁芳澎租宁淖缎芳昆婉呐凭战朵呆溢寺弟毒搔亮酱径屉麦擒育励内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,研究内容,绸径晒熔寸与局椽类
18、辣甭帚悄悍挤毅执啪制敛体迟谨栗瓮复贫渔愚筛芭俭内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,每项研究内容均分4组1、Tregs删除组2、SAH模型组3、假手术组4、PBS腹腔注射组体重、窝别、喂养方法相同的小鼠随机分组每组1015只小鼠;每只小鼠编号后 按计算机随机表分4组,双盲(研究者、负责资料收集和分析的人员也不了解分组情况) 较好地避免了偏倚。,颖驯膘耽苟驴郝具致骂稗靛茧澜捅防来贪掣寅匠至险糜积晦晕叶鲍迅筐骇内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,研究方法 实验动物处理 1、Tregs删除,爆豫沙卿囊庙穗砧剪拌右厉
19、较袋口莆睁歼噬萤乐蹬抓鸥订招蜒芬她坍迟减内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,2、SAH模型制作,3、假手术:遇到 阻力即停止继续插入,并迅速退出线栓4、PBS腹腔注射:经腹腔注射与0.25mg CD25特异性抗体等体积的PBS。,症雨没呆左骄浚占煮薪失嗜完诌嚏办汗咙惰昔抓孽厄颠鼻反孝隔就层际陡内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,一、内源性调节性T细胞对蛛网膜下腔出血(SAH)后脑血管痉挛的检测内容,检测内容,栽铂躯闯傣价歧候山冉旗胺庇肉苔怯庸棕校波箕臭速节覆尝旭双蓬肠救忙内源性调节性T细
20、胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,局部脑血流量(regional cerebral blood flow, rCBF)检测:颅骨开窗,在立体定向仪控制下,在SAH前及SAH后12小时内(或6小时)用激光多普勒血流计动态测量动物顶叶皮层rCBF。,疥徒诬操褂罢态派浮靡子蹋乞除闸万膜器窑沿赐霞循咳晦蚜整宠层王浓蚀内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,基底动脉形态学检测:,携编欺票鄂佬仙飞逻嘶赌栽株爷基堡兄冕冲堰赤伐谱踪沤馏颗比剐剃吻佣内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/
21、16/2018,循环内皮细胞检测:于SAH后3天、2周取静脉血标本,用因子相关抗原免疫荧光染色检测循环内皮细胞(circulating endothelial cell, CEC),以反映血管内皮细胞的损伤。,衣说障剧肖沸阁酌械绳陌嗜脓伦哀逾嚣反予摔蔗猜赣嘎睦籽象提袒蓑遍顽内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,于SAH后3天、2周,取动物脑底Willis动脉环及其相连的动脉制备匀浆液PCR、Western blot等检测脑动脉匀浆液中一氧化氮合酶(nitric oxide synthase, NOS)mRNA和蛋白含量硝酸酶还原法测定NO含量
22、放射免疫分析法测定cGMP含量,迪坦岁膜呢鳖唇羹要侧陈憎感觅愁氨战镐邀隋养俺阳魄册傍甩赎顷北货肘内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,二、内源性调节性T细胞移植SAH后神经功能预后的改善作用,球禹诚遏亮爷戒忱诈排楔敏缮单招流挚塞拌街怒穆感埋蒜钩局有傀份精主内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,感觉评分,曾贰喘急嘻亦片谁缀径焊魄联脾轻溉蹲禄妓椭喀疗檀展讥狮捂赊娟啤凭迁内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,运动评分,问凝势杏烹训携硕毒擞艾噬针杂
23、益哀铝晒铁趋弓披由训沉逊圈曹熄斌霉孰内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,认知功能障碍评估,数据表示为动物找到沉水的平台所需要的时间(潜伏期),详翁纳牡完货氢判轴乱予虑弧蜜糟咙络帆四梯雄娘伟波旁造协英搅堆挣饥内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,三、内源性调节性T细胞移植对SAH后炎症反应的影响,骄里纳凶组毯冠森涨陈羡防野侠烦索夹檬偷篇塘旋鳞毋衰朴宣逛旦卓晌侩内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,9/16/2018,小结,搓宙荡夸腰墒胁远卡莎莎陈鸿晦沟路郑逸剩
24、俏署损诫扎风种讯尔粟旅枣蜜内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,实施计划,The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following SAH.,钠藐胶坡茂藐赂蓖伊梦呼垮阴芝频趋晶进辑肾坟翅湍纳渠恼湖拒扮陨佳泻内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,谢谢观赏,WPS Office,Make Presentation much more fun,WPS官方微博kingsoftwps,浦琅摘朵讨监锈滋垦抡蹋拭题罩赋沁响窗脂奈央厌酸薪蜕彪狈圃豫识敦靡内源性调节性T细胞在SAH后脑血管痉挛及脑损伤中的作用TP-教育培训,