本文選題：肢體缺血再灌注 + 氧化應(yīng)激��； 參考：《中南大學(xué)》2008年碩士論文

【摘要】： 背景與目的:肢體缺血再灌注損傷臨床上極為常見,外周血管手術(shù)、肢體的創(chuàng)傷、斷肢再植術(shù)、血栓形成、腹主動(dòng)脈瘤手術(shù)、擠壓綜合征等均可引起肢體缺血再灌注損傷。近年研究發(fā)現(xiàn),肢體缺血再灌注損傷不僅影響局部缺血組織的存活和功能,而且還可造成全身炎癥反應(yīng)綜合征,累及心、肝、肺、腎、小腸、腦等遠(yuǎn)隔器官、導(dǎo)致多器官功能受損,其中以心血管系統(tǒng)的損傷最為重要。目前對(duì)肢體缺血后所致的肺,腦,肝,腸損傷機(jī)制的研究較多,對(duì)骨胳肌缺血再灌注所致心肌損傷病理生理機(jī)制,至今尚未完全闡明,大量研究表明:嚴(yán)重的肢體缺血再灌注損傷可導(dǎo)致應(yīng)激性的高血壓,應(yīng)激性心律失常,應(yīng)激性心肌缺血,心功能不全等,血紅素加氧酶-1(heme oxygenase-1,HO-1)是目前發(fā)現(xiàn)的受最多因素誘導(dǎo)的應(yīng)激蛋白。這些刺激的共同點(diǎn)是能造成氧化應(yīng)激。HO-1具有抗炎、抗細(xì)胞凋亡、抗增殖、抗氧化的性質(zhì),還有免疫應(yīng)答等方面具有重要的作用,并成為近幾年的研究熱點(diǎn)。 本實(shí)驗(yàn)應(yīng)用止血帶構(gòu)建大鼠下肢缺血再灌注模型,觀察肢體缺血再灌注后心肌病理學(xué)改變,氧化應(yīng)激機(jī)制及誘導(dǎo)型血紅素氧化酶(HO-1)的表達(dá)來說明心肌的損傷及自身保護(hù)機(jī)制。本實(shí)驗(yàn)分為兩個(gè)部分:一,觀察肢體缺血再灌注后心肌的損傷變化,并了解氧化應(yīng)激在肢體缺血再灌注后繼發(fā)的心肌損傷中的作用。二,觀察內(nèi)源性HO-1在肢體缺血再灌注后心肌中的表達(dá)變化的規(guī)律及其意義。 方法:本實(shí)驗(yàn)應(yīng)用止血帶捆扎大鼠下肢來構(gòu)造肢體缺血再灌注模型,將實(shí)驗(yàn)的大鼠隨機(jī)分為七組。即:正常組,缺血4小時(shí)再灌注2小時(shí)組,再灌注4小時(shí)組,再灌注6小時(shí)組,再灌注8小時(shí)組,再灌注16小時(shí)組,再灌注24小時(shí)組。第一部分實(shí)驗(yàn):應(yīng)用光鏡觀察心肌組織的病理變化;分別測(cè)定血清及心肌組織中的丙二醛(MDA)含量、總超氧化物歧化酶(T-SOD)活力及髓過氧化物酶(MPO)活性。第二部分實(shí)驗(yàn):應(yīng)用反轉(zhuǎn)錄—多聚酶鏈反應(yīng)(RT-PCR)檢測(cè)心肌HO-1mRNA表達(dá)的變化規(guī)律。 結(jié)果:缺血再灌注4,6小時(shí),心肌細(xì)胞明顯腫脹,肌間隙增寬,小血管充血明顯,肌間隙內(nèi)可見大量紅細(xì)胞漏出,肌間隙有核細(xì)胞明顯增多,再灌注24小時(shí)上述改變減輕。與正常組比較,血漿MDA及心肌MDA:缺血再灌注各組均明顯升高(P＜0.01),再灌注4h達(dá)高峰;血漿SOD:缺血再灌注各組均明顯下降(P＜0.01),再灌注4小時(shí)達(dá)最低值,心肌SOD:再灌注各組均明顯下降(P＜0.01),再灌注8小時(shí)達(dá)最低值;血漿及心肌MPO:缺血再灌注2h～8h出現(xiàn)明顯升高(P＜0.01),血漿MPO 4h達(dá)高峰,心肌MPO 6h達(dá)高峰,16,24h下降。肢體缺血再灌注可誘導(dǎo)HO-1mRNA在心肌表達(dá)上調(diào),與正常組比較,再灌注2h,HO-1mRNA表達(dá)無顯著變化(P＞0.05);再灌注4h,6h,8h,16h,24h后HO-1表達(dá)顯著增強(qiáng)(P＜0.01),并在16h達(dá)高峰。 結(jié)論:肢體缺血再灌注可造成心肌損傷,再灌注4-6小時(shí)心肌損傷最重,全身及心肌局部的炎細(xì)胞聚集活化,炎性因子的激活和過度的氧化應(yīng)激及氧化抗氧化失衡是肢體缺血再灌注致心肌損傷的機(jī)制,機(jī)體存在自身保護(hù)機(jī)制,活性氧族及炎性因子能上調(diào)HO-1的表達(dá),對(duì)抗氧化應(yīng)激,從而發(fā)揮心肌細(xì)胞保護(hù)作用。
[Abstract]:BACKGROUND & OBJECTIVE : Limb ischemia - reperfusion injury is very common in limb ischemia - reperfusion injury .


To observe the changes of myocardial pathology , oxidative stress and inducible heme oxygenase ( HO - 1 ) after limb ischemia - reperfusion , the effects of oxidative stress on myocardial injury following limb ischemia - reperfusion were observed .


Methods : The experimental rats were randomly divided into seven groups . The rats were randomly divided into seven groups : normal group , 4 - hour ischemia - reperfusion group , reperfusion for 4 - hour group , reperfusion for 6 - hour group , reperfusion for 8 - hour group , reperfusion for 16 - hour group and reperfusion for 24 - hour group . First part : the changes of myocardial HO - 1mRNA expression were detected by reverse transcription - polymerase chain reaction ( RT - PCR ) .


Results : After ischemia / reperfusion for 4 and 6 hours , the myocardial cells were obviously swollen , the width of the muscle was increased , the congestion of small blood vessels was significantly increased , there was a significant increase in myocardial MDA and myocardial MDA in the muscle gap ( P < 0.01 ) . After reperfusion for 4 hours , the expression of HO - 1 mRNA increased significantly ( P < 0.01 ) , and the expression of HO - 1 mRNA increased significantly after reperfusion for 4 hours , 6 h , 8 h , 16 h and 24 h ( P < 0.01 ) , and peaked at 16 h .


Conclusion : Limb ischemia - reperfusion can cause myocardial injury , reperfusion 4 - 6 hours myocardial injury heaviest , systemic and myocardial local inflammatory cell aggregation activation , inflammatory factor activation and excessive oxidative stress and oxidation resistance imbalance are the mechanism of myocardial injury caused by ischemia - reperfusion injury , the organism has its own protective mechanism , active oxygen species and inflammatory factor can regulate the expression of HO - 1 and resist oxidative stress , thus playing the protective effect of myocardial cell .
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 趙利軍;董淑云;段國(guó)賢;張連元;;氧化應(yīng)激在大鼠肢體缺血/再灌注心肌損傷中的作用[J];解放軍醫(yī)學(xué)雜志;2006年08期

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本文編號(hào)：2029883