發(fā)布時間：2019-06-19 06:55

【摘要】：目的:建立大鼠蛛網(wǎng)膜下腔出血(subarachnoid hemorrhage,SAH)模型,用褪黑素進行干預,觀察大鼠神經(jīng)行為功能變化,檢測腦海馬區(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]表達及細胞實際凋亡情況,檢測血腦通透性改變及腦水腫情況,初步探討褪黑素(melatonin,MEL)對SAH后早期腦損傷細胞凋亡的影響及其神經(jīng)保護作用機制。方法:72只健康成年雄性大鼠(300g-350g)隨機分為假手術組(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小時后免疫組化及TUNEL染色,另外8只用于腦組織含水量測量。應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小時和24小時分別腹腔注射褪黑素,觀察大鼠行為功能變化,進行神經(jīng)功能評分;48小時后處死大鼠,取顳底皮層腦組織測量腦水腫情況,檢測大鼠血腦屏障通透性變化;檢測海馬區(qū)PARP-1表達變化及細胞凋亡情況;探討褪黑素對大鼠蛛網(wǎng)膜下腔出血的神經(jīng)保護作用機制。使用SPSS13.0對數(shù)據(jù)進行統(tǒng)計分析,當p0.05認為有統(tǒng)計學意義。結果:1.神經(jīng)認知功能:與sham組相比,SAH組大鼠神經(jīng)認知功能明顯降低,食欲及活動能力明顯降低;與vehicle組比較,褪黑素治療后大鼠神經(jīng)功能明顯改善,食欲及活動能力明顯增加。2.腦組織含水量:SAH組腦組織含水量在手術后48小時明顯多于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:術后48小時SAH組大鼠顳底皮質腦組織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表達情況:術后48小時SAH組大鼠海馬區(qū)神經(jīng)元細胞PARP-1表達較sham組明顯增加有統(tǒng)計學意義(p0.01);vehicle組較SAH組PARP-1表達無明顯差異(p0.05);MEL組海馬區(qū)PARP-1表達少于vehicle組(p0.01)。5.TUNEL染色:48小時后SAH組大鼠海馬區(qū)神經(jīng)元細胞凋亡明顯多余sham組(p0.01);vehicle組較SAH組細胞凋亡無明顯差異(p0.05);但MEL組海馬區(qū)細胞凋亡少于vehicle組(p0.01)。結論: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,說明MEL可以保護血腦屏障從而緩解腦水腫。3.SAH后大鼠ARPR-1表達增加、細胞凋亡增多,使用MEL治療后PARP-1表達降低、細胞凋亡減少,說明MEL可以通過抑制PARP-1細胞凋亡通路,在SAH后EBI中降低細胞凋亡起到神經(jīng)保護作用。
[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：2502183