【摘要】：目的:建立大鼠蛛網(wǎng)膜下腔出血(subarachnoid hemorrhage,SAH)模型,用褪黑素進(jìn)行干預(yù),觀察大鼠神經(jīng)行為功能變化,檢測(cè)腦海馬區(qū)神經(jīng)元多聚腺嘌呤二核苷酸核糖聚合酶-1[Poly(ADP-ribose)poly-merase-1,PARP-1]表達(dá)及細(xì)胞實(shí)際凋亡情況,檢測(cè)血腦通透性改變及腦水腫情況,初步探討褪黑素(melatonin,MEL)對(duì)SAH后早期腦損傷細(xì)胞凋亡的影響及其神經(jīng)保護(hù)作用機(jī)制。方法:72只健康成年雄性大鼠(300g-350g)隨機(jī)分為假手術(shù)組(sham組,n=18只),蛛網(wǎng)膜下腔出血組(SAH組,n=18只),安慰劑組(vehicle組,n=18只)和褪黑素治療組(MEL組,n=18只)。再將前述各組分為兩部分,10只用于48小時(shí)后免疫組化及TUNEL染色,另外8只用于腦組織含水量測(cè)量。應(yīng)用視交叉前池一次注血法制成SAH后EBI模型,褪黑素治療組在蛛網(wǎng)膜下腔出血后2小時(shí)和24小時(shí)分別腹腔注射褪黑素,觀察大鼠行為功能變化,進(jìn)行神經(jīng)功能評(píng)分;48小時(shí)后處死大鼠,取顳底皮層腦組織測(cè)量腦水腫情況,檢測(cè)大鼠血腦屏障通透性變化;檢測(cè)海馬區(qū)PARP-1表達(dá)變化及細(xì)胞凋亡情況;探討褪黑素對(duì)大鼠蛛網(wǎng)膜下腔出血的神經(jīng)保護(hù)作用機(jī)制。使用SPSS13.0對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,當(dāng)p0.05認(rèn)為有統(tǒng)計(jì)學(xué)意義。結(jié)果:1.神經(jīng)認(rèn)知功能:與sham組相比,SAH組大鼠神經(jīng)認(rèn)知功能明顯降低,食欲及活動(dòng)能力明顯降低;與vehicle組比較,褪黑素治療后大鼠神經(jīng)功能明顯改善,食欲及活動(dòng)能力明顯增加。2.腦組織含水量:SAH組腦組織含水量在手術(shù)后48小時(shí)明顯多于sham組(p0.01);SAH組與vehicle組腦組織含水量無明顯差異(p0.05),但MEL組腦組織含水量明顯少于vehicle組(p0.01)。3.血腦屏障通透性改變:術(shù)后48小時(shí)SAH組大鼠顳底皮質(zhì)腦組織EB含量明顯多余sham組(p0.01);vehicle組與SAH組EB含量無明顯差異(p0.05);但MEL組EB含量少于vehicle組(p0.01)。4.PARP-1表達(dá)情況:術(shù)后48小時(shí)SAH組大鼠海馬區(qū)神經(jīng)元細(xì)胞PARP-1表達(dá)較sham組明顯增加有統(tǒng)計(jì)學(xué)意義(p0.01);vehicle組較SAH組PARP-1表達(dá)無明顯差異(p0.05);MEL組海馬區(qū)PARP-1表達(dá)少于vehicle組(p0.01)。5.TUNEL染色:48小時(shí)后SAH組大鼠海馬區(qū)神經(jīng)元細(xì)胞凋亡明顯多余sham組(p0.01);vehicle組較SAH組細(xì)胞凋亡無明顯差異(p0.05);但MEL組海馬區(qū)細(xì)胞凋亡少于vehicle組(p0.01)。結(jié)論:1.SAH后大鼠神經(jīng)功能缺陷明顯,經(jīng)MEL治療后大鼠神經(jīng)行為明顯改善,說明MEL可以減輕大鼠SAH后早期腦損傷,具有神經(jīng)保護(hù)作用。2.SAH后大鼠血腦通透性降低、腦水腫明顯,經(jīng)MEL治療后,大鼠血腦通透性明顯改善、腦水腫好轉(zhuǎn),說明MEL可以保護(hù)血腦屏障從而緩解腦水腫。3.SAH后大鼠ARPR-1表達(dá)增加、細(xì)胞凋亡增多,使用MEL治療后PARP-1表達(dá)降低、細(xì)胞凋亡減少,說明MEL可以通過抑制PARP-1細(xì)胞凋亡通路,在SAH后EBI中降低細(xì)胞凋亡起到神經(jīng)保護(hù)作用。
[Abstract]:Objective: to establish a rat model of subarachnoid hemorrhage (subarachnoid hemorrhage,SAH), observe the changes of neurobehavioral function, detect the expression of polyadenine dinucleotides ribose polymerase-1 [Poly (ADP-ribose) poly-merase-1,PARP-1] and the actual apoptosis of neurons in the hippocampus, detect the changes of blood and brain permeability and brain edema, and explore the changes of melatonin (melatonin,). Effect of MEL) on apoptosis in early brain injury after SAH and its neuroprotective mechanism. Methods: 72 healthy adult male rats (300g-350g) were randomly divided into three groups: sham operation group (sham group, n 鈮，

本文編號(hào)：2502183