本文選題：皮層擴(kuò)散性抑制 + 血紅蛋白　； 參考：《華中科技大學(xué)》2013年博士論文

【摘要】：皮層擴(kuò)散性抑制(Cortical spreading depression, CSD)作為偏頭痛、腦缺血以及腦外傷等多種神經(jīng)性疾病的病理學(xué)模型,對(duì)其在體發(fā)展特性的研究和了解,特別是對(duì)其引起的血液動(dòng)力學(xué)響應(yīng)和能量代謝變化的研究可以幫助人們更好的研究和治療這些神經(jīng)性疾病。多光譜光學(xué)內(nèi)源信號(hào)(Optical intrinsic signal, OIS)成像技術(shù)不僅具有較高的時(shí)間和空間分辨率,并且通過(guò)一定的數(shù)據(jù)分析處理后還可以提供多參數(shù)信息(血液動(dòng)力學(xué)、線粒體代謝以及光散射)。因此,我們利用多光譜光學(xué)內(nèi)源信號(hào)成像技術(shù)來(lái)實(shí)現(xiàn)對(duì)活體動(dòng)物(大鼠和小鼠)CSD發(fā)展過(guò)程的多參數(shù)監(jiān)測(cè)。主要研究?jī)?nèi)容如下： (1)首先介紹了多光譜OIS成像系統(tǒng),并推導(dǎo)了多光譜OIS的基本數(shù)據(jù)分析模型——修正的朗伯比爾定律,針對(duì)以前多光譜OIS數(shù)據(jù)分析過(guò)程中相關(guān)因素考慮不全面的問(wèn)題,分析了一系列與腦組織光吸收有關(guān)的生色團(tuán)(血紅蛋白,水,細(xì)胞色素c,細(xì)胞色素氧化酶,NADH和FAD),給出了這些生色團(tuán)可見(jiàn)光范圍內(nèi)的吸收光譜,并確定其是否參與多光譜OIS的數(shù)據(jù)分析,從而最終推導(dǎo)出多光譜OIS的數(shù)據(jù)分析公式,為準(zhǔn)確分析CSD相關(guān)的多光譜OIS提供方法學(xué)基礎(chǔ)。我們還模擬和分析了數(shù)據(jù)分析模型中的重要參數(shù)——差分路徑因子,定性的給出了差分路徑因子隨組織吸收、散射特性改變所產(chǎn)生的變化特征,并估計(jì)了腦組織的吸收和散射等光學(xué)特性,最后給出了可見(jiàn)光范圍內(nèi)(450-650nm)差分路徑因子隨波長(zhǎng)的變化曲線。 (2)采用多光譜OIS成像同時(shí)監(jiān)測(cè)了大鼠CSD過(guò)程中多生理參數(shù)的變化,包括氧合血紅蛋白(Oxygen-hemoglobin, HbO)、脫氧血紅蛋白(Deoxygen-hemoglobin，，HbR)、細(xì)胞色素c、細(xì)胞色素氧化酶、FAD以及光散射。發(fā)現(xiàn)CSD過(guò)程中450,470,500,530,550,570nm OIS顯示出四相變化,而600,630和650nm OIS表現(xiàn)出復(fù)雜的兩相變化。而在CSD過(guò)程中,HbO顯示出顯著的上升;HbR則出現(xiàn)下降、上升、下降的三相變化；光散射顯示了先增強(qiáng)后減弱的變化特征；細(xì)胞色素c和細(xì)胞色素氧化酶先是被還原接著又被氧化；而FAD下降然后恢復(fù)至基線值。其中HbR的上升,細(xì)胞色素c和細(xì)胞色素氧化酶的還原說(shuō)明了大鼠CSD過(guò)程中氧的供應(yīng)曾一度存在不足。發(fā)現(xiàn)在多光譜數(shù)據(jù)擬合過(guò)程中如果不考慮其它生色團(tuán)(FAD,細(xì)胞色素c和細(xì)胞色素氧化酶)和散射的變化,得到的血紅蛋白濃度變化(HbO和HbR)很可能不準(zhǔn)確。并且CSD過(guò)程中細(xì)胞色素c的變化和550nm OIS緊密相關(guān)；細(xì)胞色素氧化酶的變化和450,600,650nm OIS緊密相關(guān)；而FAD的變化和450,470nm OIS緊密相關(guān)。所以在使用這些波長(zhǎng)的OIS計(jì)算血紅蛋白變化時(shí),應(yīng)當(dāng)考慮這些生色團(tuán)的影響,從而避免HbO和HbR計(jì)算的不準(zhǔn)確。 (3)采用多光譜光學(xué)內(nèi)源信號(hào)成像系統(tǒng)研究了小鼠CSD的時(shí)變特性。30分鐘內(nèi)在小鼠腦皮層分別誘發(fā)兩次CSD,發(fā)現(xiàn)這兩次CSD顯示出不同特性：450,470,500,530,550和570nm OIS在第一次CSD中顯示出三相變化,最后幅值高于基線水平,而在第二次CSD中為四相變化；600,630和650nm OIS在第一次CSD中具有四相變化,并且最后幅值保持在低于基線值水平,600nm OIS在第二次CSD中仍具有四相變化,而630和650nm OIS在第二次CSD中只有三相變化,并且最后都能恢復(fù)到本次CSD發(fā)生之前的基線水平；HbO和總血紅蛋白(Total hemoglobin, HbT)在第一次CSD中是下降的,但在第二次CSD中是上升的；光散射在第一次CSD中先上升然后下降最后長(zhǎng)時(shí)間緩慢下降,但在第二次CSD中只有上升和恢復(fù)的變化；腦皮層大動(dòng)脈管徑在第一次CSD中有三相變化：劇烈收縮,恢復(fù)以及緩慢收縮,在第二次CSD中有四相變化：小舒張,收縮,大舒張以及恢復(fù)。而兩次CSD中還原態(tài)細(xì)胞色素c和細(xì)胞色素氧化酶的上升以及FAD的下降都說(shuō)明線粒體是處于還原狀態(tài),腦組織是處于缺氧的狀態(tài),只是第一次CSD的缺氧狀況相較于第二次CSD更為嚴(yán)重。另外,第一次CSD會(huì)引起腦皮層很長(zhǎng)時(shí)間的嚴(yán)重缺血,表現(xiàn)為HbT一直緩慢地下降,動(dòng)脈血管也緩慢而長(zhǎng)時(shí)間地收縮。 (4)研究了小鼠單側(cè)頸總動(dòng)脈結(jié)扎缺血后誘發(fā)的連續(xù)兩次CSD的發(fā)展特性,以及雙側(cè)頸總動(dòng)脈結(jié)扎缺血后小鼠自發(fā)CSD的發(fā)展特性。發(fā)現(xiàn)單側(cè)缺血小鼠第一次CSD各生理參數(shù)的變化大體上和未缺血情況類似,只是持續(xù)時(shí)間明顯變長(zhǎng),而還原態(tài)細(xì)胞色素c和細(xì)胞色素氧化酶響應(yīng)幅度變大；單側(cè)缺血小鼠第二次CSD多數(shù)生理參數(shù)的變化大體上也和未缺血情況類似,只有HbO顯示出不一致,未缺血情況下Hb0是急劇上升的,而缺血狀態(tài)下HbO有一個(gè)初始的小下降,然后小幅上升。小鼠雙側(cè)頸總動(dòng)脈結(jié)扎缺血后自發(fā)CSD的多光譜OIS表現(xiàn)為所有波長(zhǎng)統(tǒng)一的光強(qiáng)上升,而這種上升是由于散射增強(qiáng)而導(dǎo)致的。
[Abstract]:Cortical spreading depression (CSD) is a pathological model of multiple neuropathic diseases such as migraine, cerebral ischemia and brain injury. The research and understanding of its development characteristics, especially the study of hemodynamic response and energy metabolism, can help people to better study and treat it. The Optical intrinsic signal (OIS) imaging technology not only has high time and spatial resolution, but also provides multi parameter information (hemodynamics, mitochondrial thanks and light scattering) after a certain data analysis. Therefore, we use multispectral optical interior. Source signal imaging technology is used to monitor the development of CSD in living animals (rats and mice). The main contents are as follows:
(1) firstly, the multi spectral OIS imaging system is introduced, and the basic data analysis model of multi spectral OIS, the modified Longbow Bill's law, is derived. In view of the problems related to the previous multi spectral OIS data analysis, a series of chromophores (hemoglobin, water and cytochrome c) related to the optical absorption of brain tissue are analyzed. Cytochrome oxidase, NADH and FAD), give the absorption spectrum in the visible light range of these chromophores, and determine whether it participates in the data analysis of multi spectral OIS, and finally deduces the data analysis formula of multi spectral OIS, which is the basis for accurate analysis of CSD related multi spectral OIS basis. We also simulated and analyzed data analysis. The important parameter in the model, the difference path factor, qualitatively gives the variation characteristics of the difference path factor with the absorption and scattering characteristics, and estimates the optical properties of the absorption and scattering of the brain tissue. Finally, the variation curve of the 450-650nm difference path factor in the visible light range with the wavelength is given.
(2) multispectral OIS imaging was used to monitor the changes of multiple physiological parameters in CSD process in rats, including Oxygen-hemoglobin (HbO), deoxy hemoglobin (Deoxygen-hemoglobin, HbR), cytochrome c, cytochrome oxidase, FAD, and light scattering. The 450470500530550570nm OIS showed a four phase transition in the CSD process. In addition, 600630 and 650nm OIS showed complex two phase changes. In the CSD process, HbO showed a significant rise; HbR decreased, increased, and dropped three phase changes; light scattering showed a first enhanced and then weakened change; cytochrome c and cytochrome oxidase were first reduced and then oxidized; and FAD decreased then then. The rise of HbR, the reduction of cytochrome c and cytochrome oxidase showed that the oxygen supply in the rat CSD process was once insufficient. It was found that the hemoglobin obtained in the multispectral data fitting process was not considered if the other chromophores (FAD, cytochrome c and cytochrome oxidase) and scattering changes were not taken into consideration. Concentration changes (HbO and HbR) are likely to be inaccurate. And the changes in cytochrome C in CSD are closely related to 550nm OIS; the changes in cytochrome oxidase are closely related to 450600650nm OIS; and the change of FAD is closely related to 450470nm OIS. So these should be considered when using these wavelengths to calculate the changes in hemoglobin. The influence of chromophores is thus avoided to avoid inaccuracies in HbO and HbR calculations.
(3) using the multi spectral optical internal source signal imaging system to study the time-varying characteristic of mouse CSD in.30 minutes, the mouse cerebral cortex was induced two times CSD respectively. It was found that the two CSD showed different characteristics: 450470500530550 and 570nm OIS showed a three phase change in the first CSD, and the last amplitude was higher than the baseline level, but in the second CSD. For the four phase change; 600630 and 650nm OIS have four phase changes in the first CSD, and the final amplitude is kept below the baseline level. 600nm OIS still has a four phase change in the second CSD, while 630 and 650nm OIS have only three phase changes in second CSD, and finally all can be restored to the baseline level before this CSD; HbO and The total hemoglobin (Total hemoglobin, HbT) was reduced in the first CSD, but increased in the second CSD; light scattering first rose in the first CSD and dropped for the last long slow decline, but in the second CSD there was only a rise and recovery; the diameter of the cerebral cortex was three phase change in the first CSD: play Severe contraction, recovery and slow contraction, four phase changes in the second CSD: small diastolic, contraction, diastolic and recovery. While the reduction of cytochrome c and cytochrome oxidase in the two CSD and the decline of FAD both indicate that the mitochondria are in the state of reduction, the brain group is in a state of hypoxia, but the first CSD anoxia. The condition is more serious than the second CSD. In addition, the first CSD causes severe ischemia of the cerebral cortex for a long time, showing that HbT has been slow down, and the arteries of the arteries also shrink slowly and long.
(4) the development characteristics of continuous two CSD induced by unilateral carotid artery ligation and ischemia in mice and the development characteristics of spontaneous CSD after ligating the bilateral common carotid artery in mice were studied. It was found that the changes of the first CSD physiological parameters of the unilateral ischemic mice were similar to those of the non ischemic condition, but the duration was obviously longer, and the reduction state was reduced. The response amplitude of cytochrome c and cytochrome oxidase increased. The changes of most physiological parameters of second times CSD in unilateral ischemic mice were similar to that of non ischemia in general. Only HbO showed disagreement and Hb0 increased sharply in the absence of ischemia, while HbO had a small initial decrease in ischemic state and then slightly increased. The multispectral OIS of spontaneous CSD after the ligation of the common carotid artery is a uniform light intensity rising at all wavelengths, and this increase is due to the enhancement of scattering.

【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】：2013
【分類號(hào)】：R310

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