硫代乙酰胺诱导兔肝急性损害与死亡后影像学演变实验研究

发布时间：2018-04-22 21:36

本文选题：动物模型 + 急性肝衰竭　；参考：《泸州医学院》2013年硕士论文

【摘要】：第一部分： DWI评价急性药物性肝功能损害的动物实验研究目的：探讨新西兰大白兔急性化学药物性肝损伤后肝功能变化与ADC值的相关性，评价磁共振扩散加权成像（DWI）在肝功能评估中的应用价值。方法：建立新西兰大白兔急性肝损伤与衰竭模型10只，按注射硫代乙酰胺前与注射后的表现分为肝功能正常阶段组、肝功能急性损害阶段组和肝功能急性衰竭阶段组。每个阶段均采血化验ALT、AST、TBIL、PT、PTA%。每一阶段分别在b值=100，300，500，800s/mm2的条件下进行磁共振扩散加权成像，并测量各b值条件下的ADC值。以单纯抽样的方法分别从急性损害阶段和衰竭阶段各取一只进行病理检查。数据运用SPSS19.0统计软件进行分析，比较各阶段ALT、AST、TBIL、PT、PTA%的差异与各b值下ADC值的差异均采用单因素方差分析；各b值下ADC值与ALT、AST、TBIL、 PT、PTA%之间的相关性采用两因素相关性分析，双侧检验，P0.05为差异有统计学意义。结果：在600mg/kg d的剂量模式下，兔肝功能呈急性进行性障碍直至衰竭而死亡。肝功能由正常-损害-衰竭的进展中，各b值下ADC值总的变化趋势为进行性降低。b=300，500，800s/mm2时肝功能正常组与急性肝损害、肝衰竭阶段组ADC值的差异均有统计学意义，急性肝衰竭阶段ADC值较正常明显降低。急性肝损害与肝衰竭阶段组之间各b值下的ADC值差异虽无明显统计学意义，但在b=500s/mm2时两阶段组的ADC值亦有一定区别（P=0.05），其ADC值95%置信区间在肝功正常组为（1.293，1.593）×10-3mm2/s、急性肝功损害阶段组为（1.012，1.231）×10-3mm2/s、急性肝功衰竭组为（0.762,1.056）×10-3mm2/s。在b=100s/mm2时各阶段组间ADC值两两比较差异无统计学意义（P＞0.05）。各b值下ADC值与各阶段ALT、AST、TBIL、PT、PTA%的结果相关性分析表明，ADC值的下降与TBIL、PT、PTA%之间存在相关性，b值的大小对肝功能的评价有明显的影响。b＜500s/mm2时ADC值与各阶段TBIL、PT、PTA%值之间的相关系数（r）无统计学意义，b≥500s/mm2时在急性肝损害阶段ADC值的下降与TBIL的升高负相关，在急性肝衰竭阶段ADC值降低与PT的延长负相关，与PTA%下降正相关，且b值越大相关系数（r）差异越显著（P＜0.01）。但无论是低b值（b=100，300s/mm2）还是高b值（b=500，800s/mm2）时ADC值的下降与ALT、AST值的变化无明显相关性。结论：1．以TAA600mg/kg d的剂量经腹腔内注射可成功建立兔肝功能急性损害并进行性加重的动物模型。2．DWI技术可评估药物性肝损害的程度，b值的大小对肝功能的评价有差别，b=500s/mm2时的ADC值在肝功能评价中具有较好的稳定性。3.肝功能从正常-急性损害-急性衰竭期的演进过程中各b值条件下的ADC值呈进行性降低表现。4. ADC值在肝功能急性损害阶段与TBIL升高水平呈负相关，在急性肝衰竭阶段与PT的延长呈负相关与PTA%的降低呈正相关，其相关性与b值的大小有关，b≥500s/mm2时相关性明显。第二部分：基于MSCT技术虚拟尸检分析死因的动物实验研究目的：探讨急性肝衰竭死亡与心脏性猝死两类死亡模式下尸体影像学表现及其演变规律，评价MSCT技术虚拟尸检在死因分析中的应用价值。方法：以硫代乙酰胺（TAA）建立新西兰兔急性肝衰竭死亡模型8只，用kcl建立兔心脏性猝死死亡模型5只，，分别组成TAA组和DZZ组。将两组动物分别在死亡前与死后0h、6h、24h、48h、72h、96h、120h、144h、168h、192h进行64排128层螺旋CT扫描。将扫描数据送往ADW4.4工作站，采用VR、阈值分割、感兴趣区限域生长及数学形态的“腐蚀”技术分别对两组动物的脑、肺、肝进行三维容积重建成像，用灰度直方图分别统计脑、肺、肝组织容积内的像素值，以一维CT密度谱线图结合二维平面图的方式进行显示与分析。将两组动物死亡前、后各检查时间点脑、肺、肝组织的CT灰度均值用一条曲线连接起来绘成两组脑、肺、肝组织的死亡时间CT密度（TD-CT）变化曲线。数据用SPSS19.0统计学软件进行分析。比较TAA组或DZZ组各检查时间点兔脑、肺、肝组织CT均值的差异及两组各检查时间点双肺总容积值差异的均采用Games-Howell法；比较两组之间同一检查部位与检查时间点CT值的差异和肺总容积值差异均用配对t检验；以P0.05为差异有统计学意义。结果：以TAA600mg/kg d的剂量可诱使动物于72h～84h死于肝衰竭，快速静脉推注kcl可在15～20秒内使动物心跳骤停。两组死亡模式下的脑、肺、肝组织TD-CT密度曲线在死亡后的早中期阶段明显不同，各具特征：两组兔脑CT值的变化在死亡前到死亡即刻其差异具有统计学意义（P＜0.05），TAA组兔脑CT值在死亡前即已升高，死后0~24小时期间其CT值上升幅度小于DZZ组。两组兔肺组织TD-CT密度曲线及其相应的容积变化曲线有明显区别，TAA组肺组织密度呈渐进性增高，其肺容积渐进性降低，DZZ组肺组织密度早期快速增高，增高幅度大于TAA组，其肺容积早期急剧锐减。两组肺组织CT值的变化在6~24h及96h期间其差异有统计学意义（P＜0.05），DZZ组肺实变要早于TAA组且严重，TAA组肺实变缓慢。两组肺容积的变化在0~6h及72h阶段差别显著（P＜0.01）。按肺组织病理变化的过程，其CT密度曲线有六种不同的表现，分别代表肺组织CT、病理不同程度的变化，即①基本对称型曲线，表示肺组织含气良好，无明显的渗出实变影；②不对称型曲线，表示肺组织密度不均，肺内出现小片不规则的渗出实变影；③肺实变曲线Ⅰ型，表明双肺野含气区域与实变区域范围差异较大，密度高低不均；④肺实变曲线Ⅱ型，表明肺实变程度进一步加重；⑤肺实变曲线Ⅲ型，为双肺野大片均匀实变影，肺组织严重不张；⑥肺组织密度回降型曲线，表示肺组织已进入腐败阶段。两组肝组织TD-CT密度曲线及CT变化走势完全不同：TAA组肝密度随着死亡时间的延长呈进行性下降，无上升期表现；DZZ组肝密度于早期存在快速上升，中期快速下降的表现。两组肝脏CT值变化在24~120小时期间差别显著（P＜0.05）。结论：1．急性肝衰竭和心脏性猝死两类死因下的脑、肺、肝组织CT值的变化在死亡前与死亡后各具演变特征：1）急性肝衰竭模式下的脑CT值在死亡前已有增高表现，死后早期上升缓慢、变化小，中晚期逐步下降；肺CT值于死后早中期缓慢升高，晚期逐步回降，肺实质密度变化曲线从基本对称或不对称型向肺实变型曲线的Ⅰ型—Ⅱ型—Ⅲ型演变，最后出现Ⅳ型曲线；肝CT值死后无上升期，呈持续进行性下降表现。2）心脏性猝死模式下的脑CT值死后早期持续上升，变化幅度大，中晚期变化不规则；肺CT值死后早期快速升高，中晚期快速回降，肺实质密度变化曲线早期即可为肺实变型曲线的Ⅰ~Ⅲ型，无一定规律；肝CT值于死后早期持续上升，中后期曲折逐步下降。2.脑、肺、肝组织TD-CT密度曲线在早中期的演变差别明显，可以通过建立不同死亡模型下的组织TD-CT密度曲线进行死因的分析与推断。3．MSCT虚拟尸检多种成像模式在死因分析与推断中具有一定的可行性，以MSCT技术对死体多个部位、脏器进行动态的观察更利于死因的诊断。
[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.

【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R445.2;R575.3

【参考文献】