【作者】 韩佩玉；

【导师】 王米渠；

【作者基本信息】 成都中医药大学 ， 中医基础理论， 2010， 博士

【摘要】 背景将时间的年轮向前推移几年,2004年12月26日印度洋大海啸导致22.5万人丧生,这次自然灾害给人类留下了沉重的思考；震惊世界的美国“9·11”事件,则是人为灾害给人类带来的阴影；2008年5月12日的四川汶川大地震再一次敲响了警钟：灾害——将伴随着人类前进的脚步!自然灾害对于人类可以形成不同程度的伤害,不仅当事人受到直接的刺激,对其子代也会带来间接的负面影响,尤其对在个体生命关健时期的孕妇、胎儿、新生儿、婴幼儿影响最大、后果恶劣。评估和减轻地震灾害对孕妇、生产及初生、婴幼儿便成为一个迫切而严骏的现实问题。人们虽然作了不少的观察,也试图模拟地震的发生作了一些模拟地震实验,深究地震发生的机理。但在现有的模拟地震实验中,多为地球物理方面实验,难于模拟地震作生物学实验,更难于结合地震实地调查,将二者结合来研究。本文利用付出沉重代价的5·12汶川地震的人类资源,结合模拟地震的动物实验研究地震对母代及子代孕育及生理行为负面影响的危害性及严重性,探讨地震作为一种恐惧应激创伤后应激障碍(PTSD),对人类和动物的生理和行为影响的内在规律。目的①利用付出沉重代价的5·12地震资源,探讨地震对育龄妇女、孕妇及新生儿造成负面影响的特征规律,从而揭示中医“恐伤肾”所致“肾不藏精”的机理；②通过模拟地震的生物学实验,探索地震对小鼠孕育能力及仔鼠生物学特征、生长发育及行为模式的影响；③基于基因表达谱技术筛选出子代的关键差异基因,探讨“母虚及子”的分子生物学机制。方法①“肾不藏精”文献研究：历代医家对于“肾藏精”、“肾主生殖、主生长发育”、“肾为先天之本”等理论有非常丰富的研究,探讨和总结“肾”在地震等应激状态下参与机体的应激反应。②宏观母子两代的生理行为统计与分析：根据“四川省医疗保健机构住院分娩登记册”,收集5·12汶川地震极重、重、轻等7个灾区震前震后的分娩记录,应用spss13.0统计软件进行分析；同时进行模拟地震的生物学实验研究,记录小鼠母子两代的相关信息(如母代的受孕率、分娩情况及子代的出生身长、体重、尾长及生长发育情况),挖掘地震作为一种灾难性应激事件对母子两代的行为模式影响规律。③微观特征基因的芯片筛选：借助基因芯片技术,将孕期地震组子代与孕期非地震组分2组设计基因表达谱实验,利用SAS、FatiGO等多种数据库筛选地震对子代影响的特征基因表达谱及其通路的影响。结果：①69822例极重、重、轻灾区实地调查：地震对胎儿的影响程度与刺激的强度有关系,且多表现在男性比例、早产儿比例及出生缺陷比例上地震组和震后组较震前组有显著性差异,部分新生儿身长、体重也有改变。②2批6个组模拟地震实验：通过模拟地震的生物学实验的开展,发现慢性应激对小鼠生殖功能有负面影响。具体表现为孕育能力的下降、胚胎及初生小鼠生长发育迟缓、部分行为发育迟缓、免疫力低下,甚至对子代大脑的正常发育有影响。③地震应激的基因表达谱研究：机体应对应激性事件时,多个基因的表达发生改变(包括上调和下调),同时伴随着多条通路发生改变,尤其以与疾病相关的通路为最多(出生缺陷及先天性疾病)；其次为信号传导系统和内分泌免疫系统相关的通路。讨论：①模拟地震的生物学实验是可行的,拓宽了模拟地震试验的应用领域；②用中医理论来演绎“地震”对孕妇和育龄妇女的母子两代的影响规律及特征；③子代反应与多个基因的差异表达、多个通道的改变相关。更多还原

【Abstract】 BackgroundThe ring will move over a few years time, December 26,2004 Indian Ocean tsunami killed 22.5 million people, the natural disasters has left a heavy human thinking; shocked the world, "9.11" incident, it is man-made the shadow of disaster to humanity; 12 May 2008 Wenchuan earthquake has once again sounded the alarm:disaster-will be accompanied by the pace of human progress! Natural disasters, human beings can be formed for different degrees of damage, not only by direct stimulation of the parties, their offspring will also have an indirect negative impactParticularly in the period of individual life and health related pregnant women, fetuses, newborns, infants and young children most affected, the consequences of bad. Assess and mitigate earthquake disasters in pregnant women, production and new-born, infants and young children has become an urgent and serious Jun reality. Although many people made the observation, also tried to simulate earthquakes were a number of simulated earthquake test, go into the mechanism of the earthquake. However, the existing analog seismic experiments, mostly geophysical experiment, difficult to simulate earthquake for biological experiments, more difficult to transfer seismic field Investigation, to study the combination of both. This paper paid a heavy price of 5·12 Wenchuan earthquake in human resources, the simulated experimental study of earthquake seismic nurtured on mother and daughter and physiological behavior of the danger and severity of adverse effects, fear of earthquakes as a stress posttraumatic stress disorder (PTSD), on human and animal physiology and behavior of internal principles.Objectives ①Used to pay a heavy price for the 5·12 earthquake resources, earthquake revealed women of childbearing age, pregnant women and newborns have a negative impact of the characteristics of law;②Biological experiments by simulating the earthquake, seismic exploration capability and mice bred offspring biological characteristics, growth, development and behavior patterns;③Screening of the offspring based on gene expression differences in genes critical to explore the "virtual mother and child" of molecular biological mechanisms.Methods①"Kidney essence is not hidden" literatureancient, modern and contemporary to "kidney essence Zhi", "main reproductive kidney, the main growth", "as the birth of the kidney" and other kidney has a very rich theory of and research, and summary of "kidneys" in the seismic stress state involved m stress responses.②Macroscopic behavior of mother and two generations of Statistics and Analysis of PhysiologicalAccording to "health care facilities in Sichuan hospital delivery register," 5·12 earthquake to collect heavy, heavy, light, etc.7 before the earthquake disaster area after the earthquake record of delivery, application spss13.0 multi-channel analysis of statistical software; the same time to simulate seismic study of biological experiments, the mice two generations of mother and child related information, mining seismic events as a catastrophic stress on the mother and two generations of behavior studied.③Microscopic features of gene microarrayUsing gene chip technology, the offspring during pregnancy and pregnancy earthquake group 2 group of non-seismic design of gene expression profiling test components, using SAS, FatiGO + and many other databases screening effect of earthquakes on the characteristics of offspring gene expression.ResultsO field research of 69822 cases in the four degree disaster areasEarthquake on the fetus of the degree of stimulus intensity relationships, often expressed in males, premature child ratios and birth defects in the proportion of the earthquake group and after the earthquake group than before the earthquake group there were significant differences, some of neonatal length, weight also change.②six groups in two approveds of the seismic experiment Simulated earthquake by carrying out biological experiments and found that chronic stress adversely affect reproductive function in mice. Ability of specific performance marks the decline in primary mouse embryo and growth retardation, some behavioral retardation, low immunity, even for the normal development of the brain affected offspring.③Gene expression profiles of seismic stressBody response to stressful events, altered expression of many genes (including up and down), accompanied by a number of channel changes, especially disease-related pathway to a maximum of (birth defects and congenital diseases); followed for the signal transduction system and the endocrine system-related immune pathway.DiscussionO Simulated earthquake biological experiment is feasible, broaden the simulated earthquake test applications;②Interpretation using traditional Chinese medicine theory, "earthquake" for pregnant women and women of childbearing age two generations of mother-child mechanism;③Reaction and number of progeny differences in gene expression changes related to multiple channels.更多还原