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重度颈动脉狭窄模型大鼠致认知功能障碍的机制探讨
作者:郑文婧1  郄晓娟2  郑文芳3  王忠义1  王福朝1 
单位:1. 衡水市哈励逊国际和平医院 麻醉科, 河北 衡水 053000;
2. 河北医科大学第三医院 麻醉科, 河北 石家庄 050000;
3. 衡水市妇幼保健院 麻醉科, 河北 衡水 053000
关键词:颈动脉狭窄 认知功能障碍 免疫机制 细胞凋亡 
分类号:R749
出版年·卷·期(页码):2019·38·第一期(13-18)
摘要:

目的:探讨重度颈动脉狭窄致认知功能障碍大鼠模型在中枢神经和免疫功能方面的机制。方法:40只SD大鼠随机分为对照组和手术组。通过部分阻断两侧颈动脉构建重度颈动脉狭窄大鼠模型。分别于术后1、3、7 d采用Morris水迷宫实验验证认知功能障碍的诱导结果。使用ELISA检测大鼠脑组织中IL-1β、TNF-α炎性因子的表达,RT-PCR检测大鼠脑组织中TLR4、CD200的mRNA表达,TUNEL法检测大鼠脑组织的细胞凋亡情况。结果:大鼠颈动脉狭窄手术造模完成后1、3、7 d,大鼠的逃避潜伏期显著延长(F=164.800,P=0.000),穿越平台次数显著降低(F=64.430,P=0.000)。手术组大鼠在术后3 d,脑组织中的IL-1β(126.33±20.06 pg·mg-1)和TNF-α(119.88±17.31 pg·mg-1)炎性因子显著高于对照组脑组织中的IL-1β(38.25±7.73 pg·mg-1)和TNF-α(49.65±9.11 pg·mg-1)(IL-1β:t=18.320,P=0.000;TNF-α:t=16.060,P=0.000)。手术组大鼠在术后3 d,脑组织中的TLR4 mRNA(1.69±0.06)的表达水平显著高于对照组(1.00±0.04)(t=10.140,P=0.000)。手术组大鼠在术后3 d,脑组织中的CD200 mRNA(0.83±0.05)的表达水平显著低于对照组(1.00±0.04)(t=2.680,P=0.028)。手术组大鼠在术后3 d的脑组织冰冻切片TUNEL染色强于对照组。结论:TLR4、CD200介导的免疫反应和中枢神经细胞凋亡可能参与颈动脉狭窄导致认知功能障碍的发病机制。

Objective:To investigate the mechanism of central nervous system and immune function in the rat model of cognitive dysfunction induced by severe carotid stenosis. Methods:Forty SD rats were randomly assigned to control group and operation group. A rat model of severe carotid stenosis was constructed by partially blocking bilateral carotid arteries. Morris water maze tests were performed to confirm cognitive dysfunction models on day, 3 and 7 post-operation. ELISA was used to detect the expression levels of IL-1β and TNF-α in rat brain tissues. RT-PCR was used to examine the mRNA expression of TLR4 and CD200 in rat brain tissues. TUNEL method was used to detect cell apoptosis in rat brain tissues. Results:After 1 day, 3 days and 7 days after blocking bilateral carotid arteries, the escape latency of rats was significantly prolonged(F=164.800, P=0.000), and the number of crossing platform decreased significantly(F=64.430, P=0.000). 3 day after operation, the inflammatory factors of IL-1β(126.33±20.06 pg·mg-1)and TNF-α(119.88±17.31 pg·mg-1)in the brain tissues were significantly higher than those of IL-1β(38.25±7.73 pg·mg-1)and TNF-α(49.65±9.11 pg·mg-1)in the brain tissues of the control group. The differences were statistically significant(IL-1β:t=18.320, P=0.000; TNF-α:t=16.060, P=0.000). The expression level of TLR4 mRNA(1.69±0.06)in the brain tissues was significantly higher than that of the control group(1.00±0.04) 3 day after operation(t=10.140, P=0.000). The expression level of CD200 mRNA(0.83±0.05)in the brain tissues was significantly lower than that of the control group(1.00±0.04) 3 day after operation(t=2.680, P=0.028). In the operation group, TUNEL staining of frozen sections of brain tissues on the 3 day after operation was stronger than that of the control group. Conclusion:TLR4,CD200 mediated immune response and central nervous cell apoptosis may be involved in the pathogenesis of cognitive dysfunction caused by carotid artery stenosis.

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