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替米沙坦對(duì)慢性間斷性缺氧小鼠海馬CA1區(qū)氧化應(yīng)激損傷的保護(hù)作用

發(fā)布時(shí)間:2018-04-03 04:33

  本文選題:慢性間斷性缺氧 切入點(diǎn):睡眠呼吸暫停低通氣綜合征 出處:《福建醫(yī)科大學(xué)》2010年碩士論文


【摘要】: 目的:通過建立模擬睡眠呼吸暫停低通氣綜合征(Obstructive sleep apnea hypopnea syndrome OSAHS)特征慢性間斷性缺氧動(dòng)物模型,研究慢性間斷性缺氧對(duì)小鼠海馬CA1區(qū)氧化應(yīng)激損傷作用,以及替米沙坦對(duì)氧化應(yīng)激損傷的保護(hù)作用。 方法:將32只健康雄性C57B6J小鼠隨機(jī)分為CIH組、ARB替米沙坦干預(yù)組、空氣模擬對(duì)照組和空白對(duì)照組,進(jìn)行12周的模型試驗(yàn)。通過Morris水迷宮檢測小鼠空間學(xué)習(xí)及記憶能力,并用免疫組織化學(xué)方法檢測實(shí)驗(yàn)小鼠海馬CA1區(qū)NADPH氧化酶p47亞單位(p47PHOX)、8-羥基鳥苷(8-OHG)的表達(dá)情況。 結(jié)果:(1)Morris水迷宮:空間學(xué)習(xí)能力:單純?nèi)毖踅M在空間學(xué)習(xí)能力下降,經(jīng)ARB干預(yù)后可改善缺氧所致的空間學(xué)習(xí)能力的下降,不同實(shí)驗(yàn)組之間逃避潛伏期存在差別(F=3.04,P=0.045),兩兩比較發(fā)現(xiàn)CIH組與空白組(P=0.039)、空氣組(P=0.013)、ARB組(P=0.048)差別均有統(tǒng)計(jì)學(xué)差異,而ARB組與空白組(P=0.155)、空氣組(P=0.064)差別無統(tǒng)計(jì)學(xué)差異;空間記憶能力:CIH組在空間記憶能力上與空白、空氣及ARB組無差別。穿越目標(biāo)區(qū)域的次數(shù)CIH組(中位數(shù)=1,四分位間距=1.5)與空白組(中位數(shù)=3,四分位間距=2)、空氣組(中位數(shù)=2,四分位間距=1.75)、ARB組(中位數(shù)=2.5,四分位間距=3.75)組間比較無統(tǒng)計(jì)學(xué)差異(P=0.136)。(2)p47PHOX免疫組化:p47PHOX免疫組化光密度分析顯示在海馬CA1區(qū)胞質(zhì)中有陽性表達(dá),同時(shí)CIH組海馬CA1區(qū)p47PHOX表達(dá)明顯升高,經(jīng)ARB干預(yù)后海馬CA1區(qū)p47PHOX表達(dá)水平明顯下降。CIH組(中位數(shù)= 0.1463四分位間距=0.1389)與空白組(中位數(shù)=0.0067四分位間距=0.0168 )(P=0.01)空氣組(中位數(shù)=0.0062四分位間距=0.0281)(P=0.005) ARB組(中位數(shù)=0.0031四分位間距=0.0268)(P=0.005)差別均有統(tǒng)計(jì)學(xué)差異,ARB組(中位數(shù)=0.0031四分位間距=0.0268)與空白組(中位數(shù)=0.0067四分位間距=0.0168)(P=0.645)空氣組(中位數(shù)=0.0062四分位間距=0.0281)(P=0.442)。(3)8-OHG免疫組化:8-OHG免疫組化光密度分析顯示在海馬CA1區(qū)胞質(zhì)中有陽性表達(dá),同時(shí)CIH組海馬CA1區(qū)8-OHG表達(dá)明顯升高,經(jīng)ARB干預(yù)后海馬CA1區(qū)8-OHG表達(dá)水平明顯下降。CIH組(0.16±0.018)與、ARB組(0.04±0.011)(P=0.000)差別有統(tǒng)計(jì)學(xué)差異, ARB組(0.04±0.011)與空白組(0.05±0.015)(P=0.479)、空氣組(0.03±0.011)(P=0.750)差別無統(tǒng)計(jì)學(xué)差異。 結(jié)論:(1)模擬OSAHS特征的慢性間斷性缺氧可以引起小鼠腦內(nèi)NADPH氧化酶p47phox及8-OHG表達(dá)增加、學(xué)習(xí)能力下降,提示CIH可對(duì)海馬CA1區(qū)造成氧化應(yīng)激損傷,最終造成認(rèn)知功能障礙。 (2)對(duì)CIH小鼠施加替米沙坦干預(yù)后可明顯減少NADPH氧化酶p47phox及8-OHG表達(dá),并改善海馬依賴的學(xué)習(xí)能力。提示ARB對(duì)OSAHS特征的慢性間斷性缺氧所致的神經(jīng)元氧化應(yīng)激損傷具有保護(hù)作用,減輕后者所造成的功能損害。
[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.涓嶅悓瀹為獙緇勪箣闂撮,

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