替米沙坦对慢性间断性缺氧小鼠海马CA1区氧化应激损伤的保护作用

发布时间：2018-04-03 04:33

  本文选题：慢性间断性缺氧　切入点：睡眠呼吸暂停低通气综合征　出处：《福建医科大学》2010年硕士论文

【摘要】： 目的:通过建立模拟睡眠呼吸暂停低通气综合征(Obstructive sleep apnea hypopnea syndrome OSAHS)特征慢性间断性缺氧动物模型,研究慢性间断性缺氧对小鼠海马CA1区氧化应激损伤作用,以及替米沙坦对氧化应激损伤的保护作用。 方法:将32只健康雄性C57B6J小鼠随机分为CIH组、ARB替米沙坦干预组、空气模拟对照组和空白对照组,进行12周的模型试验。通过Morris水迷宫检测小鼠空间学习及记忆能力,并用免疫组织化学方法检测实验小鼠海马CA1区NADPH氧化酶p47亚单位(p47PHOX)、8-羟基鸟苷(8-OHG)的表达情况。 结果:(1)Morris水迷宫:空间学习能力:单纯缺氧组在空间学习能力下降,经ARB干预后可改善缺氧所致的空间学习能力的下降,不同实验组之间逃避潜伏期存在差别(F=3.04,P=0.045),两两比较发现CIH组与空白组(P=0.039)、空气组(P=0.013)、ARB组(P=0.048)差别均有统计学差异,而ARB组与空白组(P=0.155)、空气组(P=0.064)差别无统计学差异;空间记忆能力:CIH组在空间记忆能力上与空白、空气及ARB组无差别。穿越目标区域的次数CIH组(中位数=1,四分位间距=1.5)与空白组(中位数=3,四分位间距=2)、空气组(中位数=2,四分位间距=1.75)、ARB组(中位数=2.5,四分位间距=3.75)组间比较无统计学差异(P=0.136)。(2)p47PHOX免疫组化:p47PHOX免疫组化光密度分析显示在海马CA1区胞质中有阳性表达,同时CIH组海马CA1区p47PHOX表达明显升高,经ARB干预后海马CA1区p47PHOX表达水平明显下降。CIH组(中位数= 0.1463四分位间距=0.1389)与空白组(中位数=0.0067四分位间距=0.0168 )(P=0.01)空气组(中位数=0.0062四分位间距=0.0281)(P=0.005) ARB组(中位数=0.0031四分位间距=0.0268)(P=0.005)差别均有统计学差异,ARB组(中位数=0.0031四分位间距=0.0268)与空白组(中位数=0.0067四分位间距=0.0168)(P=0.645)空气组(中位数=0.0062四分位间距=0.0281)(P=0.442)。(3)8-OHG免疫组化:8-OHG免疫组化光密度分析显示在海马CA1区胞质中有阳性表达,同时CIH组海马CA1区8-OHG表达明显升高,经ARB干预后海马CA1区8-OHG表达水平明显下降。CIH组(0.16±0.018)与、ARB组(0.04±0.011)(P=0.000)差别有统计学差异, ARB组(0.04±0.011)与空白组(0.05±0.015)(P=0.479)、空气组(0.03±0.011)(P=0.750)差别无统计学差异。 结论:(1)模拟OSAHS特征的慢性间断性缺氧可以引起小鼠脑内NADPH氧化酶p47phox及8-OHG表达增加、学习能力下降,提示CIH可对海马CA1区造成氧化应激损伤,最终造成认知功能障碍。 (2)对CIH小鼠施加替米沙坦干预后可明显减少NADPH氧化酶p47phox及8-OHG表达,并改善海马依赖的学习能力。提示ARB对OSAHS特征的慢性间断性缺氧所致的神经元氧化应激损伤具有保护作用,减轻后者所造成的功能损害。
[Abstract]:Objective: to study the effects of chronic intermittent hypoxia on oxidative stress in the CA1 region of the hippocampus of mice by establishing an animal model of chronic intermittent hypoxia with simulated sleep apnea apnea hypopnea syndrome OSAHS.And the protective effect of telmisartan on oxidative stress injury.Methods: Thirty-two healthy male C57B6J mice were randomly divided into CIH group, air simulated control group and blank control group for 12 weeks.The spatial learning and memory abilities of mice were detected by Morris water maze, and the expression of NADPH oxidase p47 subunit p47 in the CA1 region of hippocampus of experimental mice was detected by immunohistochemical method.Results the spatial learning ability was decreased in the pure hypoxia group, and the spatial learning ability was improved by ARB intervention.涓嶅悓瀹為獙缁勪箣闂撮，

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