發(fā)布時(shí)間：2018-04-22 21:36

  本文選題：動(dòng)物模型 + 急性肝衰竭��； 參考：《瀘州醫(yī)學(xué)院》2013年碩士論文

【摘要】：第一部分： DWI評(píng)價(jià)急性藥物性肝功能損害的動(dòng)物實(shí)驗(yàn)研究 目的：探討新西蘭大白兔急性化學(xué)藥物性肝損傷后肝功能變化與ADC值的相關(guān)性，評(píng)價(jià)磁共振擴(kuò)散加權(quán)成像（DWI）在肝功能評(píng)估中的應(yīng)用價(jià)值。方法：建立新西蘭大白兔急性肝損傷與衰竭模型10只，按注射硫代乙酰胺前與注射后的表現(xiàn)分為肝功能正常階段組、肝功能急性損害階段組和肝功能急性衰竭階段組。每個(gè)階段均采血化驗(yàn)ALT、AST、TBIL、PT、PTA%。每一階段分別在b值=100，300，500，800s/mm2的條件下進(jìn)行磁共振擴(kuò)散加權(quán)成像，并測(cè)量各b值條件下的ADC值。以單純抽樣的方法分別從急性損害階段和衰竭階段各取一只進(jìn)行病理檢查。數(shù)據(jù)運(yùn)用SPSS19.0統(tǒng)計(jì)軟件進(jìn)行分析，比較各階段ALT、AST、TBIL、PT、PTA%的差異與各b值下ADC值的差異均采用單因素方差分析；各b值下ADC值與ALT、AST、TBIL、 PT、PTA%之間的相關(guān)性采用兩因素相關(guān)性分析，雙側(cè)檢驗(yàn)，P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果：在600mg/kg d的劑量模式下，兔肝功能呈急性進(jìn)行性障礙直至衰竭而死亡。肝功能由正常-損害-衰竭的進(jìn)展中，各b值下ADC值總的變化趨勢(shì)為進(jìn)行性降低。b=300，500，800s/mm2時(shí)肝功能正常組與急性肝損害、肝衰竭階段組ADC值的差異均有統(tǒng)計(jì)學(xué)意義，急性肝衰竭階段ADC值較正常明顯降低。急性肝損害與肝衰竭階段組之間各b值下的ADC值差異雖無明顯統(tǒng)計(jì)學(xué)意義，但在b=500s/mm2時(shí)兩階段組的ADC值亦有一定區(qū)別（P=0.05），其ADC值95%置信區(qū)間在肝功正常組為（1.293，1.593）×10-3mm2/s、急性肝功損害階段組為（1.012，1.231）×10-3mm2/s、急性肝功衰竭組為（0.762,1.056）×10-3mm2/s。在b=100s/mm2時(shí)各階段組間ADC值兩兩比較差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）。各b值下ADC值與各階段ALT、AST、TBIL、PT、PTA%的結(jié)果相關(guān)性分析表明，ADC值的下降與TBIL、PT、PTA%之間存在相關(guān)性，b值的大小對(duì)肝功能的評(píng)價(jià)有明顯的影響。b＜500s/mm2時(shí)ADC值與各階段TBIL、PT、PTA%值之間的相關(guān)系數(shù)（r）無統(tǒng)計(jì)學(xué)意義，b≥500s/mm2時(shí)在急性肝損害階段ADC值的下降與TBIL的升高負(fù)相關(guān)，在急性肝衰竭階段ADC值降低與PT的延長(zhǎng)負(fù)相關(guān)，與PTA%下降正相關(guān)，且b值越大相關(guān)系數(shù)（r）差異越顯著（P＜0.01）。但無論是低b值（b=100，300s/mm2）還是高b值（b=500，800s/mm2）時(shí)ADC值的下降與ALT、AST值的變化無明顯相關(guān)性。結(jié)論：1．以TAA600mg/kg d的劑量經(jīng)腹腔內(nèi)注射可成功建立兔肝功能急性損害并進(jìn)行性加重的動(dòng)物模型。2．DWI技術(shù)可評(píng)估藥物性肝損害的程度，b值的大小對(duì)肝功能的評(píng)價(jià)有差別，b=500s/mm2時(shí)的ADC值在肝功能評(píng)價(jià)中具有較好的穩(wěn)定性。3.肝功能從正常-急性損害-急性衰竭期的演進(jìn)過程中各b值條件下的ADC值呈進(jìn)行性降低表現(xiàn)。4. ADC值在肝功能急性損害階段與TBIL升高水平呈負(fù)相關(guān)，在急性肝衰竭階段與PT的延長(zhǎng)呈負(fù)相關(guān)與PTA%的降低呈正相關(guān)，其相關(guān)性與b值的大小有關(guān)，b≥500s/mm2時(shí)相關(guān)性明顯。 第二部分： 基于MSCT技術(shù)虛擬尸檢分析死因的動(dòng)物實(shí)驗(yàn)研究 目的：探討急性肝衰竭死亡與心臟性猝死兩類死亡模式下尸體影像學(xué)表現(xiàn)及其演變規(guī)律，評(píng)價(jià)MSCT技術(shù)虛擬尸檢在死因分析中的應(yīng)用價(jià)值。方法：以硫代乙酰胺（TAA）建立新西蘭兔急性肝衰竭死亡模型8只，用kcl建立兔心臟性猝死死亡模型5只，，分別組成TAA組和DZZ組。將兩組動(dòng)物分別在死亡前與死后0h、6h、24h、48h、72h、96h、120h、144h、168h、192h進(jìn)行64排128層螺旋CT掃描。將掃描數(shù)據(jù)送往ADW4.4工作站，采用VR、閾值分割、感興趣區(qū)限域生長(zhǎng)及數(shù)學(xué)形態(tài)的“腐蝕”技術(shù)分別對(duì)兩組動(dòng)物的腦、肺、肝進(jìn)行三維容積重建成像，用灰度直方圖分別統(tǒng)計(jì)腦、肺、肝組織容積內(nèi)的像素值，以一維CT密度譜線圖結(jié)合二維平面圖的方式進(jìn)行顯示與分析。將兩組動(dòng)物死亡前、后各檢查時(shí)間點(diǎn)腦、肺、肝組織的CT灰度均值用一條曲線連接起來繪成兩組腦、肺、肝組織的死亡時(shí)間CT密度（TD-CT）變化曲線。數(shù)據(jù)用SPSS19.0統(tǒng)計(jì)學(xué)軟件進(jìn)行分析。比較TAA組或DZZ組各檢查時(shí)間點(diǎn)兔腦、肺、肝組織CT均值的差異及兩組各檢查時(shí)間點(diǎn)雙肺總?cè)莘e值差異的均采用Games-Howell法；比較兩組之間同一檢查部位與檢查時(shí)間點(diǎn)CT值的差異和肺總?cè)莘e值差異均用配對(duì)t檢驗(yàn)；以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果：以TAA600mg/kg d的劑量可誘使動(dòng)物于72h～84h死于肝衰竭，快速靜脈推注kcl可在15～20秒內(nèi)使動(dòng)物心跳驟停。兩組死亡模式下的腦、肺、肝組織TD-CT密度曲線在死亡后的早中期階段明顯不同，各具特征：兩組兔腦CT值的變化在死亡前到死亡即刻其差異具有統(tǒng)計(jì)學(xué)意義（P＜0.05），TAA組兔腦CT值在死亡前即已升高，死后0~24小時(shí)期間其CT值上升幅度小于DZZ組。兩組兔肺組織TD-CT密度曲線及其相應(yīng)的容積變化曲線有明顯區(qū)別，TAA組肺組織密度呈漸進(jìn)性增高，其肺容積漸進(jìn)性降低，DZZ組肺組織密度早期快速增高，增高幅度大于TAA組，其肺容積早期急劇銳減。兩組肺組織CT值的變化在6~24h及96h期間其差異有統(tǒng)計(jì)學(xué)意義（P＜0.05），DZZ組肺實(shí)變要早于TAA組且嚴(yán)重，TAA組肺實(shí)變緩慢。兩組肺容積的變化在0~6h及72h階段差別顯著（P＜0.01）。按肺組織病理變化的過程，其CT密度曲線有六種不同的表現(xiàn)，分別代表肺組織CT、病理不同程度的變化，即①基本對(duì)稱型曲線，表示肺組織含氣良好，無明顯的滲出實(shí)變影；②不對(duì)稱型曲線，表示肺組織密度不均，肺內(nèi)出現(xiàn)小片不規(guī)則的滲出實(shí)變影；③肺實(shí)變曲線Ⅰ型，表明雙肺野含氣區(qū)域與實(shí)變區(qū)域范圍差異較大，密度高低不均；④肺實(shí)變曲線Ⅱ型，表明肺實(shí)變程度進(jìn)一步加重；⑤肺實(shí)變曲線Ⅲ型，為雙肺野大片均勻?qū)嵶冇�，肺組織嚴(yán)重不張；⑥肺組織密度回降型曲線，表示肺組織已進(jìn)入腐敗階段。兩組肝組織TD-CT密度曲線及CT變化走勢(shì)完全不同：TAA組肝密度隨著死亡時(shí)間的延長(zhǎng)呈進(jìn)行性下降，無上升期表現(xiàn)；DZZ組肝密度于早期存在快速上升，中期快速下降的表現(xiàn)。兩組肝臟CT值變化在24~120小時(shí)期間差別顯著（P＜0.05）。結(jié)論：1．急性肝衰竭和心臟性猝死兩類死因下的腦、肺、肝組織CT值的變化在死亡前與死亡后各具演變特征：1）急性肝衰竭模式下的腦CT值在死亡前已有增高表現(xiàn)，死后早期上升緩慢、變化小，中晚期逐步下降；肺CT值于死后早中期緩慢升高，晚期逐步回降，肺實(shí)質(zhì)密度變化曲線從基本對(duì)稱或不對(duì)稱型向肺實(shí)變型曲線的Ⅰ型—Ⅱ型—Ⅲ型演變，最后出現(xiàn)Ⅳ型曲線；肝CT值死后無上升期，呈持續(xù)進(jìn)行性下降表現(xiàn)。2）心臟性猝死模式下的腦CT值死后早期持續(xù)上升，變化幅度大，中晚期變化不規(guī)則；肺CT值死后早期快速升高，中晚期快速回降，肺實(shí)質(zhì)密度變化曲線早期即可為肺實(shí)變型曲線的Ⅰ~Ⅲ型，無一定規(guī)律；肝CT值于死后早期持續(xù)上升，中后期曲折逐步下降。2.腦、肺、肝組織TD-CT密度曲線在早中期的演變差別明顯，可以通過建立不同死亡模型下的組織TD-CT密度曲線進(jìn)行死因的分析與推斷。3．MSCT虛擬尸檢多種成像模式在死因分析與推斷中具有一定的可行性，以MSCT技術(shù)對(duì)死體多個(gè)部位、臟器進(jìn)行動(dòng)態(tài)的觀察更利于死因的診斷。
[Abstract]:Part one:
DWI evaluation of acute drug-induced liver injury in animals
Objective: To investigate the correlation between the changes of liver function and ADC value after acute chemical drug induced liver injury in New Zealand white rabbits, and to evaluate the application value of magnetic resonance diffusion-weighted imaging (DWI) in the evaluation of liver function. Methods: 10 rabbits with acute liver injury and failure were established. For the normal stage of liver function group, the acute liver damage stage group and the liver function acute failure stage group. Each stage was collected to test ALT, AST, TBIL, PT, PTA%. under the b value =100300500800s/mm2, respectively, and measured the ADC values under each b value. A pathological examination was taken from the acute and exhaustion stages. The data were analyzed by SPSS19.0 software. The difference of ALT, AST, TBIL, PT, PTA% and the ADC value of each b value were analyzed by single factor analysis of variance, and the correlation between ADC values and ALT under each b value was two factor correlation. Analysis, bilateral test, P0.05 was statistically significant. Results: in the dose mode of 600mg/kg D, the liver function of rabbit died of acute progressive disorder until failure. In the progression of liver function from normal damage failure, the total change trend of ADC value under each b value was the normal liver function group and the acute decrease of.B=300500800s/mm2 in the progressive lower.B=300500800s/mm2. The difference of the ADC value in the liver failure stage group was statistically significant, and the ADC value of the acute liver failure stage was significantly lower than that of the normal. The difference of the ADC value under the b values between the acute liver damage and the liver failure stage group was not statistically significant, but the ADC value of the two stage group was also different at b=500s/mm2 (P=0.05), and its ADC value was 95% confidence area. In the normal group of liver function (1.293,1.593) x 10-3mm2/s, the acute liver function damage stage group was (1.012,1.231) x 10-3mm2/s, and the acute liver failure group was (0.762,1.056) x 10-3mm2/s. at b=100s/mm2, there was no statistical difference between each stage group ADC value 22 (P > 0.05). The correlation between the decrease of ADC value and the value of TBIL, PT, PTA% has a significant influence on the evaluation of the liver function, and the correlation coefficient between ADC value and TBIL, PT, PTA% value of.B < 500s/mm2 is not statistically significant. The decrease of ADC value in the stage of acute liver failure was negatively correlated with the prolongation of PT, and was positively correlated with the decrease of PTA%, and the greater the correlation coefficient (R), the greater the b value (P < 0.01). But there was no significant correlation between the decrease of the ADC value at the low b value (b=100300s/mm2) or the high b value (b=500800s/mm2). Intraperitoneal injection can successfully establish acute damage and progressive animal model of liver function in rabbits..2.DWI technique can evaluate the degree of drug induced liver damage. The value of B value is different from the evaluation of liver function. The ADC value of b=500s/mm2 in the evaluation of liver function has good stability and.3. liver function from normal acute damage to acute failure period. In the course of the evolution, the ADC values of each b value showed progressive reduction, and the.4. ADC value was negatively correlated with the level of TBIL elevation in the stage of acute liver damage and the negative correlation with the prolongation of PT in the stage of acute liver failure and the decrease of PTA%, and the correlation was related to the size of B value, and the correlation of B more than 500s/mm2 was obvious.
The second part:
MSCT based virtual autopsy analysis of causes of death in animals
Objective: To investigate the manifestation and evolution of the autopsy in two types of death and sudden cardiac death in acute liver failure, and to evaluate the application value of the virtual autopsy in MSCT technique in the analysis of the cause of death. Method: a new death model of acute liver failure in New Zealand rabbits was established with thioacetamide (TAA), and the death die of sudden cardiac death in rabbits was established by KCl. Type TAA and DZZ groups, respectively. The two groups of animals were taken before and after death 0h, 6h, 24h, 48h, 72h, 96h, 120h, 144H, 168h, and 192h carried out 64 rows of 128 layers of spiral scanning. The scanning data were sent to the workstation, the threshold segmentation, region of interest limit growth and mathematical morphology of "corrosion" technique respectively to two groups of animals' brains, The three-dimensional volume reconstruction imaging of the lung and liver was performed. The pixel values in the volume of brain, lung and liver were calculated with gray histogram, and a one-dimensional CT density spectral line combined with two-dimensional plane map was used to display and analyze. The mean value of the CT gray level in the brain, lung and liver tissues of the two groups before the death of the animals was plotted with a curve. Two groups of brain, lung, liver tissue death time CT density (TD-CT) change curve. The data were analyzed by SPSS19.0 statistics software. The difference of the CT mean of the rabbit brain, lung and liver tissue in each time point of group TAA or DZZ group and the difference of the total volume value of the two groups at each time point were compared by Games-Howell method, and the same examination between the two groups was compared. The difference in the CT value of the site and the time point of the examination and the difference in the total volume of lung volume were both tested by paired t, and the difference between P0.05 and P0.05 was statistically significant. Results: the dose of TAA600mg/kg D could induce the animals to die of liver failure in 72h to 84h, and the rapid intravenous injection of KCl could make the animal heartbeat in 15~20 seconds. The two groups of brain, lung and liver groups in the death mode were in the group of brain, lung and liver. The TD-CT density curve of the weave was obviously different after the early and middle stage of death. It was characterized by the difference between two groups of rabbit brain CT values before death to death (P < 0.05). The CT value of rabbit brain in group TAA increased before death, and the increase of CT value was less than DZZ in 0~24 hours after death. TD-CT density in two groups of rabbit lung tissues. There were obvious differences between the curve and its corresponding volume change curve. The lung tissue density in TAA group was gradually increased, its lung volume gradually decreased, and the lung tissue density in DZZ group increased rapidly in the early stage, the increase was greater than that of the TAA group, and the lung volume decreased sharply in the early stage. The difference between the two groups of lung tissue CT values during 6~24h and 96h was statistically significant (P The pulmonary consolidation in group DZZ was earlier than that in group TAA and in group TAA, and in group TAA, the pulmonary consolidation was slow. The difference of lung volume in the two groups was significant in the stage of 0~6h and 72h (P < 0.01). According to the pathological changes of the lung tissue, there were six different manifestations of the CT density curve, representing the lung tissue CT and the pathological changes of different degrees, that is, the basic symmetry curve, expressed as the basic symmetry curve. The lung tissue has good gas and no obvious exudation. Secondly, the asymmetric curve indicates the uneven density of the lung tissue and the irregular exudation in the lung. The degree of pulmonary consolidation was further aggravated; (5) type III of the pulmonary consolidation curve, a large uniform shadow in the double lung field and severe atelectasis in the lung tissue; (6) the pulmonary tissue density back descending curve indicated that the lung tissue had entered the stage of corruption. The TD-CT density curve of the two groups of liver tissues and the changes of CT were completely different: the liver density in group TAA was progressive with the prolongation of the time of death. The liver density in the DZZ group had a rapid rise in the early stage and a rapid decline in the middle period. The changes in the CT value of the two groups were significant (P < 0.05) during the 24~120 hours (P < 0.05). Conclusion: the changes of the CT value of the brain, lung and liver tissue in 1. acute and sudden death causes of acute liver failure and sudden cardiac death were different before and after death. 1) the CT value of the brain in the model of acute liver failure has increased before death, and the early rise of the brain after death is slow, the change is small, and the middle and late stage gradually descends. The CT value of the lung rises slowly in the early and middle period after death, and the late stage of the lung is gradually descending, and the curve of the pulmonary parenchyma density changes from the type I to type II type III of the basic symmetry or non symmetric type to the pulmonary real change curve. The CT value of the liver has no rising stage after death, showing a continuous progressive decline in.2) the CT value of the brain in the mode of sudden cardiac death continues to rise in the early stage after death, the changes are large and the middle and late changes are irregular; the CT value of the lung is rapidly rising in the early post death, in the middle and late stage, and in the early stage of the pulmonary parenchyma density change curve can be the lung real in the early stage. The type I to III of the variant curve has no regularity. The CT value of the liver continues to rise in the early postmortem, and the.2. brain is gradually reduced in the middle and late stages. The TD-CT density curve of the lung and liver is different in the early and middle stages. It can be analyzed and deduced by the establishment of the TD-CT density curve under different death models to analyze and deduce the virtual autopsy of.3.MSCT. The imaging mode has a certain feasibility in the analysis and inference of the cause of death. The dynamic observation of the dead body parts and organs with MSCT technology is more conducive to the diagnosis of the cause of death.

【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R445.2;R575.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 呂發(fā)金,謝鵬,羅天友;分子影像學(xué)及其對(duì)影像醫(yī)學(xué)的影響[J];重慶醫(yī)學(xué);2005年05期

2 謝英;易旭夫;陳曉剛;周曉蓉;崔麗娟;林霞;王青;;放射影像學(xué)在頸部損傷尸體檢驗(yàn)中的應(yīng)用[J];法醫(yī)學(xué)雜志;2006年05期

3 徐同利;易旭夫;陳曉剛;;腦血管造影在法醫(yī)學(xué)尸體檢驗(yàn)中的應(yīng)用[J];法醫(yī)學(xué)雜志;2007年06期

4 張誼;張啟瑜;廖毅;楊文軍;;硫代乙酰胺劑量個(gè)體化誘導(dǎo)大鼠肝硬化門脈高壓模型[J];肝膽胰外科雜志;2007年03期

5 張美華,賈林,杜洪,蘇常青,李澤;硫代乙酰胺致大鼠肝性腦病模型的量-效關(guān)系[J];廣州醫(yī)學(xué)院學(xué)報(bào);2004年03期

6 蘇海濱;王慧芬;;關(guān)注藥物性肝衰竭[J];臨床肝膽病雜志;2012年10期

7 李一欣;丁鏘;;大鼠慢性酒精中毒模型的建立及病理學(xué)觀察[J];山東醫(yī)藥;2008年32期

8 錢曉慧,王風(fēng)云,王洪生;全身CT掃描代替尸檢解決醫(yī)療糾紛的嘗試[J];實(shí)用醫(yī)技雜志;2002年11期

9 蔡磊,王洪生,楊少平,王風(fēng)云,楊展榮;多層螺旋CT在尸檢中的應(yīng)用[J];實(shí)用中西醫(yī)結(jié)合臨床;2005年01期

10 孫振濤;韓雪萍;苗麗君;張水軍;翟文龍;宋燕;史冀華;郭文治;;腦死亡狀態(tài)巴馬小型豬肺水含量及肺超微結(jié)構(gòu)變化[J];中國(guó)組織工程研究與臨床康復(fù);2007年08期

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