雷帕霉素通过调控mTOR信号通路减轻劳力型热射病大鼠的下丘脑损伤.pdfVIP

目录

中文摘要·················································1

英文摘要·················································4

英文缩写·················································9

研究论文雷帕霉素通过调控mTOR信号通路减轻劳力

型热射病大鼠的下丘脑损伤

前言···············································10

材料与方法···············································12

结果···············································24

附图···············································28

附表···············································36

讨论···············································39

结论···············································43

参考文献··············································44

综述HPA轴与肠道菌群相互作用对热射病发生、发展的影

响·······················································48

致谢及简历···············································63

中文摘要

雷帕霉素通过调控mTOR信号通路减轻劳力型热射病大鼠

的下丘脑损伤

摘要

热射病(Heatstroke,HS)是由于机体暴露在高温高湿环境或

高强度体力活动条件下导致核心温度升高≥40.5°C及中枢神经系

统功能受损的危重病症。根据致热因素的不同,HS可分为经典

(Classicheatstroke,CHS)及劳力型(Exertionalheatstroke,EHS)。

随着全球气候变暖,超高温气候事件发生频率增加。据估计,全球

约三分之一的人口可能会受到高温的威胁。相比于CHS,EHS更

容易产生长期的神经系统的后遗症,并伴有持续存在的死亡风险。

事实上,EHS已成运动员体力活动中第三大致命原因。部队官兵中

HS发病率出现逐渐增加的趋势一项陆军官兵,HS发病的流行

病学调查显示,陆军某旅3000名士兵中,HS总发病率2.19％,

且以EHS为主,极大地制约了军队的作战能力。因此,了解HS

中枢神经系统易受损部位的损伤机制对疾病的临床治疗具有重要

意义。下丘脑室旁核(Paraventricularnucleus,PVN)是重要的中枢

神经系统易受损部位。热应激后PVN区域小细胞神经元受损,使

得机体热耐受性降低体温调节功能受损严重影响预后。研究表,,

明,热应激导致下丘脑神经元细胞坏死类似于缺血缺氧性脑病。增

强自噬可以改善脑缺血缺氧性损伤区域的神经元存活率。雷帕霉素

(Rapamycin,Rapa)可以通过调节mTOR通路和增强自噬来减轻

神经元损伤,在缺血缺氧性脑病和帕金森病中发挥作用。但是,其

对于EHS导致的下丘脑神经元损伤的作用，鲜有研究。因此,研

究Rapa在EHS中的作用以及下丘脑自噬具有重要意义。这将有

助于更好地了解EHS中枢神经损伤的作用机制,并为EHS的预

防和治疗提供新的思路。本研究通过建立EHS大鼠实验模型,观

察Rapa对EHS大鼠生存率、下丘脑组织病理学、血清中脑组织

损伤程度和脑细胞功能障碍的敏