本文選題：急性缺氧 + 腦部能量代謝��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：腦是維持機(jī)體生命活動(dòng)的重要中樞。人的大腦有約1000億個(gè)神經(jīng)元,神經(jīng)活動(dòng)所需的能量來(lái)自于腦部的供血供氧。這個(gè)龐大而復(fù)雜的系統(tǒng)的運(yùn)行機(jī)制與腦部的微循環(huán)和能量代謝密切相關(guān),受到研究人員的持續(xù)關(guān)注。隨著科學(xué)技術(shù)的發(fā)展,多種研究手段應(yīng)運(yùn)而生,從血氧與組織水平、線粒體水平、分子水平等不同層次揭示腦部能量代謝與微循環(huán)的動(dòng)態(tài)關(guān)系。能量代謝的發(fā)生在細(xì)胞內(nèi),線粒體是能量的主要加工廠。利用線粒體氧化還原呼吸鏈上位于最上游的還原型煙酰胺腺嘌呤二核苷酸(reduced nicotinamide adenine dinucleotide, NADH)的自發(fā)熒光性質(zhì),可以靈敏地檢測(cè)線粒體的氧化還原狀態(tài),從而表征細(xì)胞的能量代謝。而體循環(huán)和局部循環(huán)通常會(huì)改變腦部微循環(huán),從而影響能量代謝。因此,同步測(cè)量體循環(huán)的變化,可以對(duì)微循環(huán)變化所影響的能量代謝變化提供更全面的解釋。 本文在Chance和Mayevsky等人創(chuàng)立和發(fā)展的NADH熒光測(cè)量系統(tǒng)的基礎(chǔ)上,建立了一套新的跨層次、多參數(shù)監(jiān)測(cè)方法,實(shí)現(xiàn)了同步檢測(cè)大鼠腦皮層的NADH熒光、激發(fā)波長(zhǎng)下的反射光、腦血流流速和全身的呼吸和心電變化。為了系統(tǒng)地研究能量代謝與腦部微循環(huán)的關(guān)系,本文采用了急性缺氧的模型,并從氧在體內(nèi)傳輸和吸收的四個(gè)環(huán)節(jié)著手,分別進(jìn)行干預(yù),建立了乏氧性、血液性、循環(huán)性和組織性四類(lèi)六種急性缺氧模型,具體分析了不同因素導(dǎo)致的不同類(lèi)型缺氧發(fā)生時(shí),線粒體、微循環(huán)、體循環(huán)等多個(gè)層次的信號(hào)變化。從時(shí)間發(fā)生的先后順序可以推測(cè)能量代謝與微循環(huán)之間的相互影響。 本文的結(jié)果證實(shí)：在正常麻醉狀態(tài)下,大鼠腦皮層的代謝狀態(tài)處于66.1%-73.0%之間；在死亡時(shí),大鼠腦皮層的NADH可以上升到136.9%-151.4%；在缺氧時(shí),腦血流最高可上升至(195.5±14.9)%,而腦血容的最大增幅不超過(guò)(55.0±2.4)%。腦血流的變化幅度比腦血容大。 對(duì)于缺氧時(shí)是否出現(xiàn)毛細(xì)血管新增的這一爭(zhēng)議性問(wèn)題,本文發(fā)現(xiàn),在乏氧性和血液性缺氧的兩個(gè)模型中,缺氧發(fā)生時(shí)最先變化的是腦血容,然后才是腦血流,說(shuō)明此時(shí)的腦血容變化是毛細(xì)血管開(kāi)放數(shù)量增加造成的。 從測(cè)量的五個(gè)參數(shù)的測(cè)量結(jié)果中,本文分析了能量代謝與微循環(huán)的關(guān)聯(lián)情況。結(jié)果表明,NADH對(duì)缺氧的響應(yīng)時(shí)間與缺氧的類(lèi)型有關(guān),亦即取決于缺氧的誘因。如果僅比較局部能量代謝與微循環(huán)的關(guān)聯(lián),NADH先于腦血流/腦血容發(fā)生變化,提示能量代謝先發(fā)生變化,其次微循環(huán)產(chǎn)生自我調(diào)節(jié)作用。由于缺氧的誘因不同,NADH信號(hào)并不能保持一貫的較早響應(yīng)的優(yōu)勢(shì)。但多參數(shù)同時(shí)監(jiān)測(cè)可以彌補(bǔ)漏檢的風(fēng)險(xiǎn)。 通過(guò)對(duì)四類(lèi)六種的急性缺氧模型的研究,提示NADH參數(shù)具有一定的臨床指導(dǎo)意義,表現(xiàn)為NADH信號(hào)預(yù)警的發(fā)生比其他參數(shù)要早。如果采取合理?yè)尵?恢復(fù)供氧,機(jī)體可以免于死亡。因此,正確判斷NADH到達(dá)極值的時(shí)間和正確判斷缺氧類(lèi)型(誘因)對(duì)于臨床重癥監(jiān)護(hù)尤為重要。本文的研究提示,NADH升高到130%或進(jìn)入明顯平臺(tái)期可作為預(yù)警信號(hào)之一。由于監(jiān)護(hù)的對(duì)象和器官具有不同的氧化還原狀態(tài)性質(zhì),具體的報(bào)警水平需要進(jìn)一步的深入研究才能確定。同樣,正確判斷缺氧誘因則需要綜合多參數(shù)的變化特征來(lái)考量。
[Abstract]:The brain is an important center to maintain the life of the body. The human brain has about 100 billion neurons, and the energy required for the nerve activity comes from the blood supply and supply of oxygen in the brain. The operation mechanism of this huge and complex system is closely related to the microcirculation and energy metabolism of the brain. A variety of research means emerge as the times require. The dynamic relationship between brain energy metabolism and microcirculation is revealed from different levels of blood oxygen and tissue level, mitochondrial level and molecular level. Energy metabolism occurs in cells, mitochondria are the main processing plants of energy, and the most upstream prototyping nicotinamide is located on the upper reaches of the original respiratory chain by mitochondria oxidation. The spontaneous fluorescence properties of reduced nicotinamide adenine dinucleotide (NADH) can sensitively detect the redox state of the mitochondria and characterize the energy metabolism of the cells. The body circulation and local circulation usually change the microcirculation of the brain, thus affecting the energy metabolism. It can provide a more comprehensive explanation for the changes of energy metabolism that affect the microcirculation.
On the basis of the NADH fluorescence measurement system created and developed by Chance and Mayevsky and others, a new multilevel and multi parameter monitoring method has been established to synchronize the NADH fluorescence of the rat cerebral cortex, the reflected light at the excitation wavelength, the flow velocity of the brain and the changes of the whole body respiration and electrocardiogram. In order to systematically study the energy metabolism, the system can systematically study the energy metabolism. In relation to the microcirculation of the brain, this article adopts the model of acute hypoxia, and begins with the four links of oxygen transmission and absorption in the body. We have intervened respectively, and established four kinds of acute hypoxia models of hypoxia, blood, circulatory and tissue, and analyzed the mitochondria and microorganism of different types of hypoxia caused by different factors. Multiple levels of signal changes, such as circulation, body circulation, etc., can be used to infer the interaction between energy metabolism and microcirculation from the order of time.
The results showed that the metabolic state of the cerebral cortex was between 66.1%-73.0% and NADH in the normal anesthetic state; the cerebral cortex of the rat could rise to 136.9%-151.4% at the time of death; the maximum cerebral blood flow could rise to (195.5 + 14.9)% at the time of hypoxia, while the maximum increase of cerebral blood volume was not more than (55 + 2.4)%. It's bigger than brain blood.
For the controversial question of whether the capillaries are newly added to the hypoxia, we find that in the two models of hypoxia and blood hypoxia, the first change is the volume of brain blood, then the cerebral blood flow, indicating that the changes in the volume of brain blood are caused by the increase in the amount of capillary opening.
The relationship between energy metabolism and microcirculation was analyzed from the measured results of five parameters. The results showed that the response time of NADH to anoxia was related to the type of anoxia, that is, the inducement of hypoxia. If only the correlation between local energy metabolism and microcirculation was compared, NADH was preceded by changes in cerebral blood flow / cerebral blood volume. The energy metabolism changes first and the second microcirculation produces self-regulation. Due to the Different Inducements of hypoxia, the NADH signal does not maintain the advantage of the consistent earlier response. However, multi parameter simultaneous monitoring can make up the risk of leakage.
Through the study of the acute hypoxia model of four kinds of six kinds, it is suggested that the NADH parameter has certain clinical guiding significance, which shows that the occurrence of NADH signal early warning is earlier than the other parameters. If reasonable rescue, recovery of oxygen supply, the body can be exempt from death. Therefore, the correct judgment of the time to reach the extreme value of NADH and the correct judgement of the type of anoxia (inducement) It is particularly important for clinical intensive care. The study in this paper suggests that the rise of NADH to 130% or a clear platform can be one of the early warning signals. Due to the different redox state properties of the objects and organs of the guardianship, the specific alarm level needs further study to determine. The change characteristics of multiple parameters are required to be considered.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R742

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本文編號(hào)：1916324