TLR4/NF-κB信号通路在介导睡眠剥夺诱导膜迷路积水中的作用研究

The Role of TLR4/NF-κB Signaling Pathway in Mediating Sleep Deprivation Induced Endolymphatic Hydrops

贾玉其;胡涛;屈永涛;许夏;郭明丽

1:河北医科大学

2:河北北方学院

3:河北省人民医院耳鼻咽喉科

摘要
目的 探讨TLR4/NF-κB信号通路在介导睡眠剥夺诱导膜迷路积水中的作用。方法 选取30只健康SD大鼠,分为空白对照组、大平台对照组、睡眠剥夺2周组、睡眠剥夺3周组、睡眠剥夺4周组,每组6只。睡眠剥夺组大鼠选用改良多平台睡眠剥夺法进行造模,大平台对照组在小平台上放置网格所制大平台,空白对照组不做处理。实验前后对各组大鼠进行旷场实验评估行为学,行听性脑干反应(ABR)检测评估听力水平;ABR检测结束后腹主动脉取血,通过酶联免疫吸附实验(ELISA)法检测血清中TNF-α、MCP-1的水平;解剖耳蜗,HE染色行中阶横截面积(SM)/(中阶+前庭阶横截面积)(SM+SV)比值评价膜迷路积水情况;通过免疫组化染色检测耳蜗中IL-1β、TNF-α、MCP-1、TLR4、NF-κB P65的表达,观察实验后不同睡眠剥夺时间大鼠听力水平、膜迷路积水程度及TLR4/NF-κB信号通路相关蛋白及下游炎症因子表达水平变化规律,分析大鼠听力水平、膜迷路积水程度与TLR4/NF-κB信号通路的相关性。结果 睡眠剥夺组大鼠ABR波II反应阈升高,较空白对照组及大平台对照组均有统计学意义(P<0.01);形态学观察:空白对照组及大平台对照组积水率为0,睡眠剥夺2周组积水率为16.67%,睡眠剥夺3周组积水率为25%,睡眠剥夺4周组积水率为25%;睡眠剥夺组大鼠血清中TNF-α、MCP-1浓度均高于空白对照组及大平台对照组,其中睡眠剥夺4周组TNF-α、MCP-1浓度较空白对照组及大平台对照组均具有统计学意义;睡眠剥夺组大鼠耳蜗螺旋神经节、螺旋器、血管纹螺旋韧带IL-1β、TNF-α、MCP-1、TLR4、NF-κB P65表达均高于空白对照组及大平台对照组。结论 睡眠剥夺可能通过TLR4/NF-κB信号通路对内耳产生影响从而诱导膜迷路积水。
关键词
膜迷路积水;睡眠剥夺;TLR4/NF-κB信号通路
基金项目(Foundation):
河北省政府资助临床医学优秀人才培养项目(2020002)
作者
贾玉其;胡涛;屈永涛;许夏;郭明丽
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