本文選題：失血復合缺氧缺水缺食 + 心臟��； 參考：《中國人民解放軍軍事醫(yī)學科學院》2011年博士論文

【摘要】：目的和意義:由于爆炸恐怖襲擊、人為劣質(zhì)工程、地震災害以及事故等可造成房屋建筑垮塌,人員被掩埋,掩埋在深層廢墟內(nèi)的人員受到失血及缺氧缺水缺食等的影響,將明顯影響其生命體征和生命耐受力。心臟是對缺氧缺血較為敏感的器官之一,在失血復合缺氧缺水缺食條件下,心臟結(jié)構(gòu)和功能的改變是影響甚至決定其生命耐受力的關(guān)鍵因素。關(guān)于失血復合缺氧缺水缺食對人員心臟的影響國內(nèi)外報道極少。本研究立足于模擬災難性掩埋條件,探討失血復合缺氧缺水缺食大鼠心臟結(jié)構(gòu)與功能的損傷規(guī)律、特點及其機制,其結(jié)果對于深埋人員的及時有效救治以及生命探測與監(jiān)測儀的研制具有重要指導意義。 材料與方法:采用本課題組設(shè)計并研制的生物醫(yī)學實驗常壓低氧艙,調(diào)整艙內(nèi)氧濃度為10%(誤差0.1%),選用二級Wistar大鼠160只,隨機分為正常對照組、單純失血組、缺氧缺水缺食(三缺)組和失血復合缺氧缺水缺食(失血并三缺)組。大鼠于實驗后1d、3d、5d和7d,采用生理、生化、常規(guī)病理、超微病理、分子病理、定量病理和免疫組織化學(SP)等多種技術(shù)方法,研究失血復合缺氧缺水缺食后心臟結(jié)構(gòu)和功能改變及血清激素、細胞因子、心肌細胞凋亡相關(guān)因子在其中的作用機制。 結(jié)果: (1)外周血血象變化:三缺組和失血并三缺組WBC數(shù)在3-7 d下降;RBC與Hb先下降后增高;提示發(fā)生血濃縮,雄性更為顯著。 (2)血氣指標變化:三缺組和失血并三缺組pO2、pCO2明顯進行性下降,PH值3d后降低,雄性尤為顯著。 (3)大鼠血清心肌酶譜的改變:單純失血組血清LDH、CK明顯降低,AST無明顯變化;三缺組AST、LDH和CK均先降低后升高;失血并三缺組可加重LDH、CK的變化。 (4)血清電解質(zhì)的變化:三缺組和失血并三缺組血清Na+、K+、Ca2+呈增高趨勢。 (5)細胞因子的改變:三缺組和和失血并三缺組傷后大鼠血清IL-6先降低后增高,TNFα暫時性升高,IL-1變化較輕微。 (6)血漿激素的變化:三缺組和失血并三缺組傷后1d可致ACTH先升高后降低;7d時皮質(zhì)醇明顯升高,上述變化尤以失血并三缺組更為明顯。 (7)大鼠心臟結(jié)構(gòu)改變:單純失血組和三缺組心臟的基本病變?yōu)樾募〖毎冃浴⒌蛲�、壞�?肌纖維排列紊亂、斷裂、溶解,線粒體腫脹、嵴消失,基質(zhì)均質(zhì)狀;內(nèi)質(zhì)網(wǎng)擴張,脫顆粒;糖原顆粒減少;血管內(nèi)皮細胞凋亡;病變于1d~7d呈進行性加重;當三缺復合失血時上述損傷明顯加重。其病變具有速發(fā)性、進行性、全心性和部位差異性特點(左心重于右心,心室重于心房,內(nèi)層重于中外層,心肌細胞重于蒲肯野細胞)。 (8)三種致傷組于各時間點心肌細胞凋亡指數(shù)改變:單純失血組、三缺組和失血并三缺組心肌細胞凋亡指數(shù)于1d～7d均顯著高于正常對照組(P0.05,P0.01),其中失血并三缺組于早期(1d)較其他兩組最為明顯;于3-7d增高幅度呈降低趨勢,提示可能與心肌細胞壞死增多有關(guān); (9)凋亡相關(guān)因子的改變:于各時間點Bax和Caspase-3表達均呈增強、MOD值增高趨勢,其中失血并三缺組較失血組和三缺組于早期更為明顯;Bcl-2均呈表達減弱、MOD值降低趨勢,尤其5-7d時較明顯;上述凋亡相關(guān)因子表達變化呈現(xiàn)失血并三缺組依次較三缺組、單純失血組加重趨勢。 (10)ERK信號轉(zhuǎn)導通路相關(guān)因子的變化: p-CREB和RKIP于各時間點均基本呈不同程度增強、MOD值增高,其中失血并三缺組較失血組和三缺組于早期更為明顯;p-ERK則均表達減弱、MOD值降低,尤其5-7d時較明顯。 上述(9)和(10)結(jié)果提示,凋亡相關(guān)因子變化及ERK信號轉(zhuǎn)導通路相關(guān)因子異常均參與心肌細胞凋亡的發(fā)生發(fā)展過程。 結(jié)論:在模擬掩埋條件下大鼠發(fā)生失血復合缺氧缺水缺食后:(1)心臟血清心肌酶譜等功能發(fā)生明顯異常;(2)心肌組織學和超微結(jié)構(gòu)發(fā)生嚴重損傷,心肌細胞凋亡指數(shù)顯著增高;上述病變具有速發(fā)性、進行性、全心性和部位差異性特點;(3)心臟功能異常和心肌結(jié)構(gòu)損傷重于和快于單純失血和缺氧缺水缺食組;血清細胞因子和激素的異常參與其損傷的病理生理過程。(4)心肌細胞促凋亡因子Bax表達增加,抑凋亡因子Bcl-2表達減少相關(guān),Bcl-2/Bax比值下降,表達失衡,并進一步通過線粒體途徑,釋放細胞色素C,激活Caspase-3,引發(fā)心肌細胞凋亡。(5)ERK信號轉(zhuǎn)導通路相關(guān)基因表達異常(RKIP和p-CREB表達增加,p-ERK表達減少等),參與心肌細胞凋亡的發(fā)生發(fā)展過程。
[Abstract]:Objective and significance: due to the explosion of terrorist attacks, artificial poor engineering, earthquake disasters and accidents, people are buried in the buried, buried in the deep ruins of the blood loss and hypoxia, water shortage and lack of food, which will obviously affect their vital signs and life tolerance. The heart is more sensitive to hypoxia and ischemia. One of the organs, the changes in the structure and function of the heart are the key factors that affect or even determine their life tolerance under the condition of the complex anoxia and lack of water and lack of food. The influence of blood loss and lack of water and lack of food on the heart of the people is rarely reported. The damage laws, characteristics and mechanism of the heart structure and function of the rat are of great guiding significance for the timely and effective treatment of the deep buried personnel and the development of the life detection and monitoring apparatus.
Materials and methods: the oxygen concentration in the normal pressure hypoxic chamber designed and developed by our group was 10% (0.1%), and 160 rats of grade two Wistar rats were selected and randomly divided into normal control group, simple blood loss group, anoxia and water deficiency (San Que) group and blood loss and lack of water and lack of food (blood loss and three deficiency) in the group. After 1D, 3D, 5D and 7d, a variety of technical methods, such as physiological, biochemical, pathological, ultrapathological, molecular pathology, molecular pathology, quantitative pathology and immunohistochemistry (SP), were used to study the changes of cardiac structure and function and the mechanism of serum hormone, cytokine and cardiomyocyte apoptosis related factors after blood loss complex anoxia and lack of water and lack of food.
Result:
(1) peripheral blood hemogram changes: three the number of WBC in the deficient group and the group with blood loss and three deficiency decreased at 3-7 D; RBC and Hb first decreased and then increased; suggesting that blood concentration is more significant for males.
(2) changes in blood gas index: three in group pO2 and pCO2 in group three and three respectively.
(3) the change of serum myocardial enzyme spectrum in rats: the serum LDH, CK decreased obviously in the simple blood loss group, and there was no obvious change in AST. Three the deficiency group was AST, LDH and CK decreased first, and the loss of blood and three deficiency could aggravate the changes of LDH and CK.
(4) changes in serum electrolytes: three, serum Na+, K+ and Ca2+ increased in the absence group and the three group with blood loss.
(5) cytokine changes: three in the absence group, and three in the group with blood loss and three deficiency, the serum IL-6 decreased first and then increased, while TNF alpha increased temporarily, and the change of the serum level was slight.
(6) changes in plasma hormone: three deficiency group and loss of blood and three deficiency group, 1D can cause ACTH to increase first and then decrease, and the cortisol increases obviously at 7d, especially in the group of hemorrhagic and three deficiency.
(7) changes in the cardiac structure of rats: the basic pathological changes in the heart of the pure blood loss group and the three deficiency group were the degeneration, apoptosis and necrosis of the cardiac myocytes, the disorder of the muscle fibers, the breakage, dissolution, the swelling of mitochondria, the disappearance of the crista, the homogenization of the matrix, the endoplasmic reticulum dilation, degranulation, the decrease of glycogen granules, the apoptosis of the vascular endothelial cells, and the progressive aggravation of the 1d~7d; when three; when lesion was progressively aggravated in the vascular endothelial cells; when three, when the lesion was progressively aggravated; when three, when the lesion was progressively aggravated; when the lesion was aggravated; when three was aggravated; when the lesion was aggravated; when the lesion was aggravated; when three became aggravated; when the lesion was aggravated; when three aggravated; when the lesion was progressively aggravated; when three, when the lesion was progressively aggravated; when three, when the lesion was aggravated; when three became progressively aggravated; when the lesion was aggravated The damage of these injuries is obviously aggravated. The lesion has the characteristics of rapid onset, progressive, full heart and site difference (left heart is heavier than right heart, ventricle weighs the atrium, inner layer is heavier than Chinese and foreign layer, and cardiac myocytes are heavier than the Purkinje cells).
(8) the change of apoptotic index of cardiac myocytes at all time in three kinds of injury groups: pure blood loss group, three deficiency group and three deficiency group of 1D ~ 7d were significantly higher than that of normal control group (P0.05, P0.01), among which, blood loss and three deficiency group were most obvious in the early stage (1D) than those in the other two groups, and the increase of 3-7d was decreasing. It can be related to the increase of necrosis of cardiac myocytes.
(9) the changes of apoptosis related factors: the expression of Bax and Caspase-3 increased at all time points, and the MOD value increased, in which the loss of blood and the three deficiency group were more obvious than those in the early stage of the loss group and the three deficiency group; the expression of Bcl-2 decreased and the MOD value decreased, especially in 5-7d; the expression of apoptosis related factors presented in the group of hemorrhagic and three deficiency groups. In the less than three group, the simple blood loss group aggravated the trend.
(10) the changes of ERK signal transduction pathway related factors: p-CREB and RKIP were basically enhanced at various time points, and the value of MOD increased, in which the blood loss and the three deficiency group were more obvious than those in the bleeding group and the three group at the early stage, and the p-ERK expression decreased and the MOD value decreased, especially when 5-7d was more obvious.
The above (9) and (10) results suggest that changes in apoptosis related factors and abnormalities in ERK signal transduction pathway related factors are involved in the occurrence and development of cardiomyocyte apoptosis.
Conclusion: under the simulated burial condition, the rat blood loss complex anoxia and lack of water and lack of food: (1) the cardiac serum myocardial enzyme spectrum and other functions were obviously abnormal; (2) the myocardial histology and ultrastructure were seriously damaged and the apoptosis index of myocardial cells increased significantly; the above pathological changes have the characteristics of rapid onset, progressive, whole heart and location difference; (3) heart The abnormality of the dysfunction of the organs and the damage of the myocardial structure were more important than that of the simple loss of blood and anoxia and lack of water, and the abnormalities of serum cytokines and hormones involved in the pathophysiological process of the injury. (4) the expression of apoptosis factor Bax increased, the expression of anti apoptotic factor Bcl-2 decreased, the ratio of Bcl-2/Bax decreased, the expression was unbalance, and further passed through Mitochondrial pathway, release cytochrome C, activate Caspase-3 and induce cardiomyocyte apoptosis. (5) abnormal expression of ERK signal transduction pathway related gene expression (RKIP and p-CREB expression increase, p-ERK expression decrease, etc.), and participate in the development and development of cardiomyocyte apoptosis.

【學位授予單位】：中國人民解放軍軍事醫(yī)學科學院
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R363

【參考文獻】

相關(guān)期刊論文 前10條

1 張暉;顧興華;徐丹令;孫愛軍;夏蓓莉;劉雯;王克強;左O;葛均波;;大鼠急性心肌梗死后缺血缺氧心肌早期凋亡信號分子的變化[J];復旦學報(醫(yī)學版);2007年04期

2 馮兵;周小波;楊旭;葉自林;何作云;;凋亡誘導因子介導缺氧/復氧致肥大心肌細胞凋亡的作用[J];生理學報;2006年06期

3 宋華培;顏洪;黨永明;褚志剛;張瓊;黃躍生;;磷脂酰肌醇3激酶抑制劑LY294002對缺血缺氧心肌細胞的作用研究[J];現(xiàn)代生物醫(yī)學進展;2007年11期

4 葛興利,李小迪,張煥萍,趙昆;肺心病急性發(fā)作期腎素、血管緊張素、醛固酮及心鈉素、血氣的臨床研究[J];陜西醫(yī)學雜志;2000年05期

5 吳紅萍,陳雁冰,羅佩玨;慢性阻塞性肺疾病患者低氧血癥對血清心肌酶譜的影響[J];中國實用內(nèi)科雜志;2002年02期

6 張勇,張薇,時慶德,李靜先,陳家琦;急性運動心肌缺氧對大鼠心肌纖維和線粒體膜結(jié)構(gòu)及功能的影響[J];天津體育學院學報;1997年01期

7 陳鳴和，蔡孔長，，蔣仲蓀，徐正惠，朱金昌;慢性常壓缺氧高二氧化碳對大鼠心肺功能與結(jié)構(gòu)的影響[J];溫州醫(yī)學院學報;1994年04期

8 耿新林;沈海麗;;慢性肺心病血清心肌酶變化與缺氧的關(guān)系[J];中國社區(qū)醫(yī)師;2009年05期

9 李尚儉,陳新義,田文華,姜馨;慢性心力衰竭患者血漿腎上腺皮質(zhì)激素及心鈉素的含量及分析[J];心血管康復醫(yī)學雜志;2005年03期

10 吳大方;周泉;劉曉宇;周巖;劉秦原;;心絞痛患者血漿醛固酮濃度變化的研究[J];心血管康復醫(yī)學雜志;2006年03期

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