【摘要】：目的通過(guò)建立大鼠熱射病模型,并對(duì)熱射病大鼠進(jìn)行Morris水迷宮實(shí)驗(yàn)觀察其行為學(xué)及對(duì)其海馬組織進(jìn)行全基因寡核苷酸芯片檢測(cè),探討熱射病后大鼠的認(rèn)知功能變化及認(rèn)知損害的可能發(fā)生機(jī)制。方法建立熱射病大鼠動(dòng)物模型監(jiān)測(cè)平均動(dòng)脈壓(mean arterial pressure,MAP)及核心體溫(core temperature,Tc),熱射病模型建立成功后于熱射病第7天進(jìn)行Morris水迷宮試驗(yàn)評(píng)價(jià)熱射病后認(rèn)知功能改變情況。之后對(duì)熱射病大鼠的海馬組織與對(duì)照組大鼠海馬組織進(jìn)行全基因組寡核苷酸芯片檢測(cè)并比對(duì)分析。結(jié)果1,幾乎所有大鼠在核心體溫達(dá)42℃以上時(shí)口唇有粉紅色分泌物,即發(fā)生了嚴(yán)重的肺水腫。熱射病模型組造模44只,死亡16只,成活率53.6%。熱射病7天后大鼠的學(xué)習(xí)和記憶能力是減退的。2,對(duì)大鼠海馬組織進(jìn)行全基因寡核苷酸芯片檢測(cè)發(fā)現(xiàn)差異基因表達(dá)不同有統(tǒng)計(jì)學(xué)上意義的共有188個(gè)。在這些表達(dá)的差異基因中,其中有99的基因表達(dá)是增高的,有89的基因表達(dá)是下降的。在對(duì)這188個(gè)差異基因進(jìn)行通路分析中發(fā)現(xiàn),絲裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信號(hào)途徑涉及的基因高達(dá)7個(gè)(Jun,Hspa1a,Hspa1b,Hspa11,Hspb1,I11b,Ddit3)。表達(dá)明顯下降的有Pde9a基因,其編碼的PDE9A是一種對(duì)c GMP有高親和力的特異性磷酸二酯酶(phosphodiesterases,PDE),其通過(guò)選擇性的抑制c AMP或c GMP的水解,從而參與學(xué)習(xí)記憶障礙等中樞神經(jīng)系統(tǒng)疾病的調(diào)節(jié)。表達(dá)明顯下降的還有Cxcl12基因,它編碼的趨化因子CXCL12又稱為基質(zhì)細(xì)胞衍生因子-1(stromal cell derived factor,SDF-1),在神經(jīng)細(xì)胞的遷移、調(diào)控神經(jīng)遞質(zhì)的釋放及調(diào)節(jié)海馬神經(jīng)元突觸可塑性上有至關(guān)重要的作用。再者,表達(dá)顯著下調(diào)的Sema4f基因,其編碼的Sema4F蛋白是Semaphorin家族中的一員。Sema4F在神經(jīng)元細(xì)胞軸突導(dǎo)向、軸突分支的調(diào)節(jié)及海馬神經(jīng)元細(xì)胞突觸的聯(lián)系及突觸可塑性的維持有重要作用。同時(shí)表達(dá)顯著下調(diào)的有Slit2基因,其編碼的蛋白與Semaphorins蛋白一樣都是軸突導(dǎo)向因子家族,在軸突的生成、軸突間突觸的聯(lián)系及突觸的塑性與重建均有重要作用。此外,Cspg4基因也是顯著下調(diào)的差異表達(dá)基因的,其編碼的硫酸軟骨素蛋白多糖4(chondroitin sulfate proteoglycan4,CSPG4)是中樞神經(jīng)系統(tǒng)細(xì)胞外基質(zhì)中(extracellular matrix,ECM)的重要組成成分,在中樞神經(jīng)系統(tǒng)的發(fā)育及維持成熟后的神經(jīng)系統(tǒng)的正常功能發(fā)揮重要作用。另外,還有一種顯著上調(diào)的差異基因Hmox1基因,其編碼的血紅素氧合酶-1(heme oxygenase-1,HO-1)是血紅素降解的起始酶和限速酶,通過(guò)抗氧化、抗炎和抗凋亡而有保護(hù)細(xì)胞的作用。結(jié)論1,熱射病7天后大鼠的學(xué)習(xí)記憶能力下降。2,熱射病對(duì)腦部損害廣泛而嚴(yán)重,MAPK信號(hào)傳導(dǎo)通路系統(tǒng)可能參與了熱射病對(duì)海馬損害的過(guò)程。3,Pde9a基因、Cxcl12基因、Cxcl12基因、Slit2、Cspg4等基因的下調(diào)可能是熱射病后學(xué)習(xí)和記憶功能損害過(guò)程中起著重要的作用。
[Abstract]:Objective to establish a rat model of heat radiation disease and to observe its behavior by Morris water maze test and to detect the whole gene oligonucleotide microarray in the hippocampus of the rats with heat radiation disease. Objective: to investigate the changes of cognitive function and the possible mechanism of cognitive impairment in rats with heat radiation disease. Methods the mean arterial pressure (mean arterial pressure,MAP) and core body temperature (core temperature,Tc) were measured in an animal model of heat radiation disease rats. The changes of cognitive function were evaluated by Morris water maze test on the 7th day after the successful establishment of the heat radiation disease model. Then the whole genome oligonucleotide microarray was used to detect and analyze the hippocampal tissue of the heat-emitting disease rats and the control group. Results 1. When the core body temperature was above 42 鈩，

本文編號(hào)：2469233