【摘要】：目的:研究神經(jīng)調(diào)節(jié)素-1β(neuregulin-1β,NRG-1β)對(duì)腦出血(intracerebral hemorrhage,ICH)血腫組織周圍超氧化物歧化酶(Superoxide dismutase,SOD)和醌氧化還原酶(NADPH:quinine oxidoreductase,NQO1)表達(dá)的影響,評(píng)估腦水腫和神經(jīng)功能障礙程度,進(jìn)而探討NRG-1β在腦出血的神經(jīng)保護(hù)作用及機(jī)制。方法:選取健康雄性SD大鼠58只,采用立體定位尾狀核注射Ⅳ型膠原酶建立大鼠腦出血模型。假手術(shù)組12只雄性SD大鼠,按上述方法同位置注射生理鹽水。成功制備48只腦出血模型大鼠納入統(tǒng)計(jì)學(xué)范圍,隨機(jī)分成模型組、NRG-1β治療組(2ug/kg),每組24只。每組再分為兩個(gè)時(shí)間點(diǎn):24h、72h,根據(jù)各時(shí)間點(diǎn)再分為兩個(gè)亞組。假手術(shù)組每個(gè)亞組各6只大鼠,模型組和NRG-1β治療組每個(gè)時(shí)間點(diǎn)12只。術(shù)后按既定時(shí)間點(diǎn)分別處死大鼠,采用改良的神經(jīng)功能缺損評(píng)分法(modified neurological severity score,m NSS)評(píng)估各組大鼠神經(jīng)功能障礙程度,應(yīng)用干-濕重法測(cè)定ICH后腦組織含水量,免疫印跡、免疫組化分別檢測(cè)大鼠腦血腫周圍組織抗氧化酶SOD、NQO1的表達(dá)水平。結(jié)果:1.與假手術(shù)組相比,模型組和NRG-1β治療組腦組織含水量明顯增多在大鼠ICH后24h和72h時(shí)間點(diǎn),有統(tǒng)計(jì)學(xué)意義(P0.05)。NRG-1β治療組各時(shí)間點(diǎn)腦組織含水量與模型組相比降低,統(tǒng)計(jì)學(xué)分析有意義(P0.05),提示NRG-1β能夠減輕ICH急性期腦水腫程度。2.與假手術(shù)組相比,模型組和NRG-1β治療組神經(jīng)功能障礙明顯在大鼠ICH后24h和72h時(shí)間點(diǎn),有統(tǒng)計(jì)學(xué)意義(P0.05)。與模型組同時(shí)間點(diǎn)比較,NRG-1β治療組神經(jīng)功能障礙程度明顯減輕,統(tǒng)計(jì)學(xué)分析有意義(P0.05),表明NRG-1β能夠改善ICH急性期神經(jīng)功能障礙。3.各組大鼠腦血腫周圍組織免疫結(jié)果顯示,假手術(shù)組僅在進(jìn)針部位可見(jiàn)散在分布的單個(gè)SOD、NQO1陽(yáng)性顆粒細(xì)胞表達(dá),各時(shí)間點(diǎn)比較無(wú)明顯差異。在24h和72h時(shí)間點(diǎn)模型組和NRG-1β治療組可觀察到在大鼠ICH周圍組織表達(dá)明顯的SOD、NQO1陽(yáng)性顆粒,以神經(jīng)元細(xì)胞、小膠質(zhì)細(xì)胞、中性粒細(xì)胞等多見(jiàn)。與模型組相比,NRG-1β治療組相同時(shí)間點(diǎn)SOD、NQO1陽(yáng)性顆粒數(shù)量更顯著,差異有統(tǒng)計(jì)學(xué)意義(P0.05),表明在ICH急性期,NRG-1β能夠上調(diào)抗氧化酶SOD、NQO1表達(dá)。4.各組大鼠腦血腫周圍組織Western Blot檢測(cè)結(jié)果顯示,模型組和NRG-1β組均可見(jiàn)較亮的SOD、NQO1蛋白條帶影在大鼠ICH后24h和72h時(shí)間點(diǎn)。與假手術(shù)組相比,模型組和NRG-1β治療組各時(shí)間點(diǎn)SOD、NQO1相對(duì)蛋白灰度值均較高(P0.05),差異有統(tǒng)計(jì)學(xué)意義。NRG-1β治療組各時(shí)間點(diǎn)SOD、NQO1相對(duì)蛋白灰度值高于模型組,統(tǒng)計(jì)學(xué)分析有意義(P0.05),表明NRG-1β在大鼠ICH后急性期能夠上調(diào)抗氧化酶SOD、NQO1水平。結(jié)論:在ICH損傷急性期,NRG-1β能夠增加抗氧化酶SOD、NQO1水平,減少自由基生成,減輕氧化應(yīng)激,顯著改善腦水腫及神經(jīng)功能障礙,發(fā)揮神經(jīng)保護(hù)作用。
[Abstract]:Objective: to study the effect of neuregulin-1 尾 (neuregulin-1 尾 -NRG-1 尾) on the expression of Superoxide dismutase (Superoxide dismutase) and NADPH:quinine oxidoreductase (NADPH:quinine) NQO1, and to evaluate the degree of brain edema and neurological dysfunction in patients with intracerebral hemorrhage. To explore the neuroprotective effect and mechanism of NRG-1 尾 in intracerebral hemorrhage. Methods: 58 male Sprague-Dawley rats were selected and intracerebral hemorrhage model was established by injection of type 鈪，

本文編號(hào)：2197274