【作者】 王典；

【导师】 于晓军；

【作者基本信息】 汕头大学 ， 病理学与病理生理学， 2005， 硕士

【摘要】 背景与目的: 我们总结了多年的法医病理学鉴定案例中,发现严重创伤后常规救治5d以上死亡者,主要死因大多为继发的MODS,而原发性损伤大多得到不同程度的修复或痊愈。迄今,严重创伤导致MODS的机制尚未完全阐明,主要有:缺血-再灌注假说、细菌毒素假说、胃肠道假说、炎症失控假说、两次打击假说、微循环障碍假说、代谢改变假说和基因调控假说。其中均未涉及创伤后急性TE缺乏问题。已有报道,重伤可引起TE一定程度的缺乏,Se等TE补充,可减少重伤患者继发SIRS、二次感染及MODS的发生率,缩短住院时间,降低死亡率。提示给予TE补充性治疗可预防MODS的发生。鉴于TE具有诸多重要生理功能,特别是临床上仍未见相应的常规补充。我们推测,重度创伤后引发的机体急性TE缺乏可能成为导致院内感染和MODS发生率高的因素之一。但是,关于严重创伤后TE如何缺乏及其与院内感染和MODS之间关系的研究很少,尚未见相关的实验研究报道。 本课题,旨在模拟人类严重创伤的实际情况,在无麻醉情况下,选择远离重要内脏的肢体建立标准化家兔重伤模型,观察伤后家兔血及内脏组织TE含量及其相关酶和产物的变化规律,以期初步阐释重伤后机体TE变化与MODS和死亡之间的可能相关机制。材料与方法: 建立ISS=22的重伤家兔模型,随机分为重伤组28只和正常对照组6只,其中重伤组有7只家兔分别于伤后4-6d死亡,归为死亡组。重伤组中采血组动物按伤前、伤后12h、36h、60h、6d、9d、14d、20d、28d定时采血,测血Se含量、GPx活性及血清MDA含量,处死组动物伤后12h、60h、6d、14d、28d分批处死,检测血及相关脏器TE及其他相关指标;测脑、心、肝、肺组织中Zn含量及心、肝脏GPx活性、MDA含量。心组织透射电镜观更多还原

【Abstract】 Background and Objective:Our practice in forensic pathology identification in recent years revealed that the cause of death in traumatic patients died in five days after admission was MODS, and original injuries of them have been treated and recovered in certain degree. Up to now, Mechanisms of MODS occurrence in trauma were not fully clarified. Many hypothesises were proposed including "ischemia-reperfusion hypothesis", "bacteria and toxin hypothesis", "gastrointestinal hypothesis ", " inflammation un-control hypothesis", " gene induced hypothesis", "twice attack and double phase pre-stress hypothesis" ,etc. However, TE deficiency had not been involved in these mechanisms. There had been reported that severe trauma result in TE deficiency to certain degree, and that Se supplementation in these patients remarkably reduced the rate of the secondary infection, MODS and mortality, which indicated that Se and other TE supplementation in these patients may act important effect on preventing the happen of MODS. Considering the important physiologic functions of TE, and the fact that regular supplemented measure of TE in clinical had not been implemented in these patients, we persumed that TE deficiency in severe traumatic patients may be one of a crucial factor that lead to hospital onset infectio and MODS. However, there was few research about severe trauma result in acute TE deficiency and the relationship between this deficiency and high incidence of hospital onset infection, MODS. The study established a severe traumatic animal model by injuring the limb and subcutaneous tissue which far away from vital organs under none anaesthesia to observethe change law of TE, relative enzyme and its product in blood and visceral to analyze the relationship between these change and MODS occurrence.Materials and Methods:Severe traumatic rabbits model with ISS=22 was established. And 34 rabbits were randomly devided into two groups, one is control group with 6 rabbits and another one is traumatic group with 28 rabbits. There were 7 rabbits in severe traumatic rabbits which classified as dead group. All rabbits were phlebotomized from ear-edge vein before trauma and 12h, 36h, 60h, 6d, 9d, 14d, 21 d after the trauma at about 9:00 AM, and detect its Se content, GPx activity and MDA content. The rabbits were excuted group by group in 12h, 36h, 60h, 6d, 14d, 28h after the trauma, and TE content in vital organs and GPx activity, MDA content in liver and heart had been detected. Electron microscope investigation were performed in heart tissue in 3d after trauma. 2,3-Diaminonaphthalene fluorescent analysis was used to determine Se in blood, and atomic absorption spectrophotometric flame method was applied in those of tissue. Detection of GPx, MDA in blood and tissue were used chromatometry and TBA method respectively.Result:1 General manifestation of severe traumatic rabbit and histologic observation of their visceral organsThe severe traumatic rabbits refused to eat and drink in 24h post-trauma, and body weight loss in progress in 1 week after trauma. Movement of injuried limbs was seriously limited, but there were no infection and active bleeding in wound. There were 7 rabbits dead with mortality of 35%. Histologic and morphologic changes in executed rabbits mainly included slight congestion , a few focus of infection and light hydropic degeneration, and the change aggravated in 1 week aftere trauma. In death rabbit, the visceral organs exhibited evident acute damage including expanding, diffuse congestion in lung, brain, heart, liver, kidney and dispersed gray necrosis focus in liver. Main histologic pathological were showed as parenchyma cellular edema, little necrosis focus and inflammatory infiltration. Grited alteration in brain tissue, acute alveolar serum exudation, cardiac muscle fiber wavy deformation, hepatic cord dissolution, Renal glomerulus hyaline change, proximal convoluted tubule epithelia granular are swelling and renal tubule emphraxis and so on can be observed. Ultramicrostructure observing in electronmicroscope showed that myofibril structure became blur and mitochondrial swelled slightly in 1st day after trauma, and obvious vague in myofibril structure with high mitochondrial swelling on 3rd day post-trauma.2 Change of Se content, GPx activity in blood, MDA content, biochemical indicator in serum in traumatic rabbitsSe content in blood decreased remarkably in 6 days after trauma, and still under normal from 7th to 14th day post-trauma, and it reached to normal level in 3rd week. GPx activity in blood decrease significantly in 7 days after trauma, and tend to normal level on about 7th day after trauma. MDA content beginned to increase on 3 rd day and reached to peak on 6th day after trauma, It maintained in normal level from 9th day to 21st day after trauma. The change of Se content and GPx activity in blood were correlated. Compared to none-death rabbit, death rabbit had lower Se content and GPx activity in blood and higher MDA content in serum in stated time after trauma, but the difference is insignificant.AS1\ G\ BUN all elevated continually in death rabbits after trauma, In non-death rabbits, serum’s AST and ALT increase slightly in 3 days after trauma , and then recovered to pre-trauma level. However, serum’ Cr and BUN fluctuate and had no significant increase ordecrease post- trauma.3 Se content, GPx activity and MDA content in relative organs after traumaSe content in liver increase gradually in 3 day after trauma, and then recovered to normallevel by degrees. Se content increased slightly in brain, and decreased lightly in lung after trauma, but fluctuated in heart. GPx activity in liver post-trauma decrease firstly and then increase, and in heart tend to decrease in general. MDA content in liver after trauma increase firstly and then increase, and change of MDA content in heart contrary to that of liver generally.Conclusion:1 Severe traumatic rabbit modle which caused to acute TE deficiency with mortality of 35% was successfully established. Biochemical indicator of AST> O\ ALT, BUN in severe traumatic rabbits accord to MODS ,and pathologic change in brain, heart, lung,liver and kidney accord to MOF which suggested that death mechanism is MODS in severe traumatic rabbit.2 Se content and GPx activity decrease in stage, and MDA content increase in periodly, time of lower Se content and GPx activity and higher MDA content are similar to death time aftertrauma indicated that acute TE deficiency in traumatic rabbits may participate in MODSoccurrence.3 Se content in liver change larger and liver may be the most important organ to modulate Semetabolism in trauma.更多还原