本文選題：外傷性蛛網(wǎng)膜下腔出血(TSAH) + 酗酒�。� 參考：《汕頭大學(xué)》2007年碩士論文

【摘要】： 背景與目的 外傷性蛛網(wǎng)膜下腔出血(traumatic subarachnoid haemorrhage，TSAH)約占無顱骨骨折時(shí)顱內(nèi)出血的90％。早在1963年國外學(xué)者報(bào)道了酗酒后TSAH死亡案例中，多是顏面或頸部遭受拳擊等輕微暴力，導(dǎo)致致死性TSAH，而不合并其他顱腦損傷，或僅伴有輕微腦挫傷。但是，關(guān)于TSAH發(fā)生機(jī)制及其與酗酒關(guān)系和參與度，國內(nèi)外尚無統(tǒng)一認(rèn)識(shí)，亦未見系統(tǒng)研究報(bào)道，一定程度上影響了此類案件的法醫(yī)學(xué)死因分析鑒定和審判量刑。 本文目的是在本課題組已經(jīng)建立的大鼠灌酒后TSAH模型基礎(chǔ)上進(jìn)一步實(shí)驗(yàn)，擬觀察急慢性酗酒時(shí)腦組織tPA及MMP-9表達(dá)情況，以期從毒理學(xué)、組織病理學(xué)及分子生物學(xué)角度闡述TSAH發(fā)生和死亡的相關(guān)機(jī)制。 材料與方法 健康雄性SD大鼠，體重250～350g，隨機(jī)分為急性單純灌酒組和急性灌酒后打擊組，每組7只；慢性單純灌酒組和慢性灌酒后打擊組，每組17只；對照為灌水打擊組，每組5只。實(shí)驗(yàn)組予食用白酒北京二鍋頭(56％v／v)灌胃，急性灌酒組一次性灌酒劑量為15ml／Kg；慢性灌酒組連續(xù)灌酒1個(gè)月、每天兩次間隔8h，，前2周灌酒量8ml／kg／次、后2周12ml／kg／次。對照組灌同劑量純凈水。急性組灌酒后2h、慢性組最后一次灌酒后2h，用自制單擺式定位定量腦損傷打擊裝置復(fù)制大鼠腦震蕩性損傷模型，急性灌酒打擊組分別于打擊后0.5h、2h、4h、6h、12h斷頭處死取血，慢性灌酒組打擊后2h斷頭處死，對照組處死時(shí)間比照實(shí)驗(yàn)組相應(yīng)時(shí)間段。 觀察灌酒后大鼠生命體征變化，檢測血乙醇濃度，觀察腦組織形態(tài)學(xué)變化及tPA、MMP-9表達(dá)情況。采用SPSS統(tǒng)計(jì)軟件和Excel數(shù)據(jù)庫處理和統(tǒng)計(jì)分析實(shí)驗(yàn)數(shù)據(jù)。 結(jié)果 1動(dòng)物醉酒行為觀察 大鼠灌酒后短時(shí)間內(nèi)興奮性較強(qiáng)、不停走動(dòng)，步態(tài)不穩(wěn)，約0.5h后逐漸出現(xiàn)急性酒精中毒臨床表現(xiàn)：側(cè)臥、昏睡、翻正反射消失，呼吸緩慢，血壓降低(P＜0.05)。灌酒組與灌水組大鼠血壓在打擊后呈現(xiàn)一過性短暫性血壓升高(P＜0.05)，呼吸未見改變。慢性組大鼠灌酒2周后，毛發(fā)粗糙暗淡、精神萎靡，進(jìn)食量減少；3周后體重較對照組增長緩慢(P＜0.05)，4周后基礎(chǔ)血壓升高(P＜0.05)。 2酒精濃度檢測 急性組大鼠灌酒后2h血乙醇濃度達(dá)最高峰值188.8±5.8 mg／dl，之后逐漸降低，12h降至1.7±0.5 mg／dl。 3 TSAH發(fā)生率及死亡率 急性灌酒組TSAH發(fā)生率為28.6％，死亡率為0，自發(fā)性SAH發(fā)生率為0。慢性灌酒組TSAH發(fā)生率為82.4％，死亡率為58.8％；自發(fā)性SAH發(fā)生率為5.9％，死亡率為0。 4 HE染色觀察 急性灌酒組大鼠傷后各時(shí)間段大鼠腦組織形態(tài)學(xué)表現(xiàn)為不同程度輕度淤血、腫脹。組織學(xué)觀察，腦蛛網(wǎng)膜疏松淤血水腫，薄層片狀蛛網(wǎng)膜下腔出血，多見于腦干腹側(cè)區(qū)，神經(jīng)元及小膠質(zhì)細(xì)胞輕度水變性(顆粒性腫脹)。 慢性灌酒組大鼠腦組織形態(tài)學(xué)表現(xiàn)為不同程度中至重度淤血、腫脹，不同程度蛛網(wǎng)膜下腔出血。組織學(xué)觀察，腦蛛網(wǎng)膜疏松淤血水腫，大片蛛網(wǎng)膜下腔出血，神經(jīng)元中重度水變性，細(xì)胞周隙擴(kuò)大，可見神經(jīng)元核固縮、數(shù)量減少，膠質(zhì)細(xì)胞增生明顯。 5免疫組織化學(xué)染色觀察 正常大鼠腦組織tPA表達(dá)微弱，急性灌酒組及打擊后各時(shí)間段腦海馬、小腦、枕葉tPA陽性細(xì)胞數(shù)表達(dá)高于灌水打擊對照組，tPA和MMP-9陽性細(xì)胞表達(dá)的光密度值亦均高于對照組(P＜0.05)。其中，6h組表達(dá)高于0.5h組(P＜0.05)。但是，額葉與對照組無統(tǒng)計(jì)學(xué)差異。 慢性灌酒組腦組織各區(qū)域tPA陽性細(xì)胞數(shù)及光密度值表達(dá)均強(qiáng)于對照組(P＜0.01)，MMP-9光密度值高于對照組(P＜0.01)。急慢性灌酒組及其相應(yīng)打擊組大鼠腦組織tPA、MMP-9表達(dá)無明顯差異(P＞0.05)。 結(jié)論 1建立了穩(wěn)定的大鼠急慢性灌酒后外傷性蛛網(wǎng)膜下腔出血模型，證實(shí)了灌酒后輕微頭部暴力打擊與TSAH高發(fā)生率及死亡率相關(guān)，首次實(shí)驗(yàn)證實(shí)了慢性灌酒大鼠TSAH、SAH發(fā)生率及死亡率均明顯高。 2證實(shí)了長期慢性灌酒大鼠基礎(chǔ)血壓升高，灌酒后血壓照灌酒前降低，打擊后血壓呈一過性升高，容易發(fā)生血管破裂出血。 3證實(shí)了急性和慢性灌酒組大鼠腦組織海馬、小腦、枕葉中tPA與MMP-9陽性細(xì)胞數(shù)和光密度值均較對照組表達(dá)增強(qiáng)，提示損傷早期腦組織tPA可大量釋放，繼而通過MMP-9造成對血管壁結(jié)構(gòu)破壞，促進(jìn)出血。大量長期飲酒后tPA、MMP-9過度表達(dá)對神經(jīng)元具有致壞死作用。尚未見同類研究報(bào)道。 此外，tPA一直被臨床用作SAH和腦血栓急性期治療藥物。本實(shí)驗(yàn)結(jié)果提示在酒后TSAH的救治時(shí)，應(yīng)盡量減少tPA的釋放并對其活性加以抑制，降低再次出血的危險(xiǎn)。同時(shí)，注意減少和避免神經(jīng)元不可逆損傷的發(fā)生。
[Abstract]:Background and Purpose






Traumatic subarachnoid hemorrhage ( TSAH ) accounts for 90 % of the intracranial hemorrhage in the absence of skull fracture . In 1963 , foreign scholars reported that there were mild violence such as boxing and other minor violence , leading to fatal TSAH without merging other brain injury , or with mild brain contusion . However , there was no uniform understanding at home and abroad about the mechanism of TSAH and its relationship with alcohol and alcohol .






The aim of this paper is to further experiment on the model of TSAH , which has been established in the study group , and to observe the expression of the tissue and MMP - 9 in brain tissue during acute and chronic alcoholism , with a view to elaborating the mechanism of TSAH ' s occurrence and death from toxicology , histopathological and molecular biology .






Materials and Methods






Male SD rats weighing 250 - 350g were randomly divided into acute pure alcohol group and acute alcohol - infused group , each group was 7 rats .
17 rats in each group ;
In the control group , 5 rats in each group were divided into two groups : the experimental group was given edible white spirit Beijing two - pot head ( 56 % v / v ) , and the dose of one - time infusion was 15ml / Kg .
In the control group , the rats were killed at 0.5 h , 2 h , 4 h , 6 h , 12 h , and the control group was killed for 2 h after the last time . The control group was killed for 2 h and the control group was killed for a period of time compared with the experimental group .






The changes of vital signs in rats were observed , the concentration of ethanol was detected , the morphological changes of brain tissues and the expression of tissue morphology , and the expression of MMP - 9 were observed . SPSS statistical software and Excel database were used to analyze and analyze the experimental data .






Results






An Observation on the Behavior of Drinking Wine in 1 Animal






The results showed that the blood pressure of the rats was decreased ( P & lt ; 0 . 05 ) . After 2 weeks , the hair was rough , the spirit was depressed , and the consumption of food was decreased .
After 3 weeks , the body weight was slower than that in the control group ( P & lt ; 0.05 ) , and the basic blood pressure increased after 4 weeks ( P & lt ; 0.05 ) .






2 . Determination of alcohol concentration






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本文編號：2105569