本文選題：腦梗死 + 磁共振擴(kuò)散張量成像　； 參考：《鄭州大學(xué)》2013年碩士論文

【摘要】：背景和目的 腦梗死是缺血性腦血管病(ischemic cerebro vascular disease, ICVD)的嚴(yán)重表現(xiàn)形式,是臨床中樞神經(jīng)系統(tǒng)最常見的疾病之一。隨著社會(huì)老齡人口的增加,其發(fā)病率呈逐漸上升趨勢(shì),約占全部腦血管疾病的80%左右[2]。其高死亡率、高致殘率及易復(fù)發(fā)性嚴(yán)重影響著人類的健康和生活質(zhì)量,給社會(huì)及家庭帶來巨大的精神和經(jīng)濟(jì)負(fù)擔(dān)。近年來的研究發(fā)現(xiàn),幕上局灶性的腦損傷也可引起遠(yuǎn)隔區(qū)域(丘腦、小腦等)的功能改變,磁共振成像(：magnetic resonance imaging, MRI)上可以表現(xiàn)為表觀擴(kuò)散系數(shù)和部分各向異性指數(shù)的改變。多數(shù)學(xué)者認(rèn)為其發(fā)生機(jī)制可能與神經(jīng)機(jī)能聯(lián)系不能學(xué)說有關(guān)。腦梗死后交叉性小腦神經(jīng)機(jī)能聯(lián)系不能(crossed cerebellar diaschisis, CCD)是指幕上腦梗死導(dǎo)致對(duì)側(cè)小腦半球血流量的降低,進(jìn)而引起對(duì)側(cè)小腦半球神經(jīng)元活性下降及新陳代謝障礙的現(xiàn)象。大多學(xué)者認(rèn)為此現(xiàn)象與皮質(zhì)-橋腦-小腦(cortical-pons-cerebellum, CPC)通路的損傷有關(guān)。另外也有學(xué)者認(rèn)為此現(xiàn)象與患者小腦血流動(dòng)力學(xué)改變和遲發(fā)性小腦神經(jīng)元死亡有關(guān)。 磁共振彌散張量成像(diffusion tensor imaging, DTI)是在磁共振擴(kuò)散加權(quán)成像(diffusion weighted imaging, DWI)的基礎(chǔ)上基于平面回波成像(echo planar imaging, EPI)技術(shù)發(fā)展起來的一種新的、無創(chuàng)、可視化觀察體內(nèi)水分子微觀擴(kuò)散運(yùn)動(dòng)的磁共振成像的新技術(shù),其通過測(cè)量水分子擴(kuò)散的程度和方向來反映腦梗死后表觀擴(kuò)散系數(shù)及部分各向異性指數(shù)的改變,可以為腦梗死的早期診斷和治療提供重要的參考價(jià)值。 本研究采用改良的Longa線栓法,建立重復(fù)性高、穩(wěn)定性強(qiáng)的大腦中動(dòng)脈阻塞(middle cerebral artery occlusion, MCAO)模型。采用磁共振擴(kuò)散張量成像技術(shù),對(duì)大鼠腦MCAO后不同的時(shí)間點(diǎn)(1h、3h、6h、9h、12h、24h和72h)不同部位腦組織的表觀擴(kuò)散系數(shù)及部分各向異性分?jǐn)?shù)情況進(jìn)行檢測(cè),并與免疫組織化學(xué)檢測(cè)與磁共振檢查相應(yīng)時(shí)間點(diǎn)、相應(yīng)部位腦組織RGMa蛋白的表達(dá)對(duì)照。以此探討：1、DTI參數(shù)值在MCAO后遠(yuǎn)隔區(qū)域不同時(shí)間點(diǎn)的擴(kuò)散變化,從而為應(yīng)用DTI技術(shù)來評(píng)價(jià)腦梗死后神經(jīng)機(jī)能聯(lián)系不能提供理論依據(jù)和實(shí)驗(yàn)基礎(chǔ)。2、大鼠腦梗死后小腦改變的病理變化及其與磁共振信號(hào)改變的相關(guān)性。3、腦梗死后神經(jīng)機(jī)能聯(lián)系不能的相關(guān)機(jī)制。 材料與方法 1、選取健康SD大鼠70只,體重為260g-300g,平均(286.2+8.9)g；將70只大鼠隨機(jī)分為兩組：實(shí)驗(yàn)組56只,參照Longa法建立左側(cè)大鼠MCAO模型；對(duì)照組14只,僅暴露左側(cè)的大腦中動(dòng)脈,不插入線栓。 2、采用美國(guó)GE公司HDxt3.0T高場(chǎng)磁共振掃描機(jī)和大鼠專用線圈,對(duì)照組和實(shí)驗(yàn)組大鼠分別采集橫軸位T1加權(quán)成像(T1-weighted imaging, T1WI)和T2加權(quán)成像(T2-weighted imaging, T2WI)、矢狀位T2WI、DWI及DTI。依據(jù)磁共振橫軸位T2WI掃描層面,在每個(gè)時(shí)間點(diǎn)分別選取2只大鼠,然后將鼠腦組織切成3mm厚的切片,運(yùn)用免疫組化檢測(cè)大鼠腦缺血梗死核心及遠(yuǎn)隔部位小腦RGMa蛋白的表達(dá)情況。 3、觀察并記錄左側(cè)大腦半球梗死核心(基底節(jié)區(qū))及雙側(cè)小腦半球腦組織在DWI圖像上隨時(shí)間的變化情況,并記錄不同時(shí)間點(diǎn)腦擴(kuò)散參數(shù)包括表觀擴(kuò)散系數(shù)(apparent diffusion coefficient, ADC)和部分各向異性指數(shù)(fractional anisotropic, FA)。比較1h、3h、6h、9h、12h、24h和72h實(shí)驗(yàn)組左側(cè)基底節(jié)區(qū)和雙側(cè)小腦半球與正常對(duì)照組ADC值和FA值是否存在差異,及其隨時(shí)間點(diǎn)的變化曲線。比較不同時(shí)間點(diǎn)實(shí)驗(yàn)組對(duì)側(cè)小腦半球FA值與RGMa蛋白表達(dá)的相關(guān)性。 4、采用SPSS17.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料采用X±SD表示。正常對(duì)照組與MCAO組計(jì)量資料比較采用兩隨機(jī)樣本t檢驗(yàn),影像學(xué)與病理學(xué)指標(biāo)的相關(guān)性采用Spearnman相關(guān)分析。以P0.05表示差異具有統(tǒng)計(jì)學(xué)意義。 結(jié)果 1、大鼠MCAO后1h基底節(jié)ADC值、FA值開始降低,12h降至最低,后有所回升,但仍低于對(duì)照組。大鼠MCAO后各個(gè)時(shí)間點(diǎn)左側(cè)基底節(jié)區(qū)及雙側(cè)小腦半球與正常對(duì)照組相比,ADC值和FA值降低,均具有統(tǒng)計(jì)學(xué)差異(P0.05)。雙側(cè)小腦ADC值及FA值的變化趨勢(shì)與梗死核心區(qū)一致。梗死對(duì)側(cè)小腦半球ADC值及FA值較梗死同側(cè)小腦半球下降程度較大。 2、腦缺血后不同時(shí)相RGMa蛋白在左側(cè)基底節(jié)區(qū)的表達(dá)均有所增加,可見棕黃色的RGMaP日性著色。局灶性腦缺血后1h RGMa P日性細(xì)胞在病灶區(qū)不斷聚集,24h達(dá)高峰,RGMa陽性表達(dá)數(shù)目增多最為明顯,在隨后的72h內(nèi)稍有下降,但與正常對(duì)照組相比仍持續(xù)高表達(dá)。雙側(cè)小腦半球RGMa蛋白表達(dá)與梗死核心區(qū)變化相似。梗死對(duì)側(cè)小腦RGMa蛋白表達(dá)平均灰度值較梗死同側(cè)小腦半球高。在對(duì)照組大鼠脈絡(luò)叢、血管周圍、小腦浦肯野細(xì)胞及腦干神經(jīng)元中均可見RGMa蛋白陽性表達(dá)。 3、遠(yuǎn)隔部位RGMa蛋白表達(dá)上調(diào)與FA值下降呈負(fù)相關(guān)(P0.05,r=-0.341)。 結(jié)論 1、幕上腦梗死后遠(yuǎn)隔區(qū)域可以發(fā)生神經(jīng)機(jī)能聯(lián)系不能現(xiàn)象。 2、遠(yuǎn)隔部位擴(kuò)散參數(shù)隨幕上梗死核心變化而變化,間接說明神經(jīng)機(jī)能聯(lián)系不能現(xiàn)象可能與神經(jīng)傳導(dǎo)通路有關(guān)。 3、腦缺血后,軸突導(dǎo)向分子RGMa蛋白的表達(dá)上調(diào),說明RGMa參與軸突再生與修復(fù)過程。 4、雙側(cè)小腦半球RGMa蛋白和磁共振擴(kuò)散參數(shù)的變化證實(shí)交叉性小腦神經(jīng)機(jī)能聯(lián)系不能存在。
[Abstract]:Background and purpose
Cerebral infarction is a serious manifestation of ischemic cerebrovascular disease (ischemic cerebro vascular disease, ICVD). It is one of the most common diseases of the clinical central nervous system. With the increase of the aging population of the society, the incidence of the cerebral infarction is increasing gradually, accounting for about 80% [2]. of all cerebrovascular diseases, high mortality, high disability rate and easy recurrence. Sex has a serious impact on human health and quality of life and brings great spiritual and economic burden to the society and family. In recent years, it has been found that the supratentorial brain damage can also cause functional changes in the distant regions (:magnetic resonance imaging, MRI), and can be shown as apparent diffusion system. Changes in the number and partial anisotropy index. Most scholars believe that the mechanism of its occurrence may be related to the inability of the neurologic connection. The cross cerebellar neurologic connection after cerebral infarction (crossed cerebellar diaschisis, CCD) refers to the reduction of the half of the cerebellum by the supratentorial cerebral infarction, which leads to the half of the cerebellum. Most scholars believe that this phenomenon is related to the damage to the cortical-pons-cerebellum (CPC) pathway. In addition, some scholars believe that this phenomenon is related to the changes in the hemodynamics of the cerebellum and the delayed cerebellar deity of the cerebellum.
Magnetic resonance diffusion tensor imaging (diffusion tensor imaging, DTI) is a new, noninvasive, visually observed magnetic resonance imaging of the microdiffusion motion of water molecules in the body based on the magnetic resonance diffusion weighted imaging (diffusion weighted imaging, DWI) based on the plane echo imaging (echo planar imaging, EPI) technology. Technology, by measuring the degree and direction of water molecular diffusion, reflects the apparent diffusion coefficient and the change of partial anisotropy after cerebral infarction, which can provide important reference value for the early diagnosis and treatment of cerebral infarction.
In this study, a modified Longa thread thrombus method was used to establish a high repeatability and stable middle cerebral artery occlusion (MCAO) model. The apparent diffusion coefficient and part of the brain tissue in different parts of the rat brain (1H, 3h, 6h, 9h, 12h, artery) were measured by magnetic resonance diffusion tensor imaging (MR diffusion tensor imaging). Detection of the heterosexual fraction, and compared with the expression of RGMa protein in the corresponding parts of the brain tissue with the corresponding time points of immunohistochemistry and magnetic resonance examination and the expression of RGMa protein in the corresponding parts of the brain. This is to discuss the diffusion of the parameters of the 1, DTI parameters at different time points in the distant region, so that the application of DTI to evaluate the neurologic connection after cerebral infarction can not be mentioned. For the theoretical basis and experimental basis.2, the pathological changes of the cerebellar changes after cerebral infarction and the correlation with the change of MRI signal.3, and the related mechanism of the neurologic function after cerebral infarction.
Materials and methods
1, 70 healthy SD rats were selected, with a weight of 260g-300g and an average of (286.2+8.9) g, and 70 rats were randomly divided into two groups: the experimental group was 56, and the Longa method was used to establish the left rat MCAO model. The control group was only exposed to the left middle cerebral artery and did not insert the thread thrombus.
2, the GE HDxt3.0T high field MRI scanner and the rat special coil were used, the control group and the experimental group were used to collect the transverse axis T1 weighted imaging (T1-weighted imaging, T1WI) and T2 weighted imaging (T2-weighted imaging, T2WI), and the sagittal position T2WI. 2 rats were selected and the rat brain tissue was cut into 3mm thick slices. The expression of RGMa protein in the nucleus of cerebral ischemia and the cerebellum in the distant part of the rat was detected by immunohistochemistry.
3, observe and record the changes in the DWI images of the left cerebral hemisphere infarct core (basal ganglia) and bilateral cerebellar hemisphere, and record the parameters of brain diffusion at different time points including the apparent diffusion coefficient (apparent diffusion coefficient, ADC) and the partial anisotropy index (fractional anisotropic, FA). Compare 1H, 3h, The ADC values and FA values of the left basal ganglia and bilateral cerebellar hemispheres in the experimental group of 6h, 9h, 12h, 24h and 72h were different, and their FA values were different, and their curves of change with time. The correlation between the FA value of the lateral cerebellar hemisphere and the expression of RGMa protein in the experimental group at different time points was compared.
4, statistical analysis was carried out with SPSS17.0 statistical software, and the measurement data were expressed in X + SD. The normal control group and the MCAO group were compared with the two random sample t test, and the correlation between the imaging and pathological indexes was analyzed by Spearnman correlation analysis. P0.05 indicated that the difference had the significance of unified planning.
Result
1, the ADC value of 1H basal ganglia after MCAO in rats was reduced, 12h decreased to the lowest, and then recovered, but it was still lower than that of the control group. The left basal ganglia and bilateral cerebellar hemisphere at each time point after MCAO were lower than the normal control group, the ADC value and FA value decreased, all of which were statistically different (P0.05). The trend of the bilateral cerebellar ADC value and FA value and the infarction were the stem. The ADC values and FA values in the contralateral cerebellar hemisphere were larger than those in the ipsilateral cerebellar hemisphere.
2, after cerebral ischemia, the expression of RGMa protein in the left basal ganglia increased, and brown yellow RGMaP diurnal coloring. After focal cerebral ischemia, 1H RGMa P daily cells gathered in the focus area, 24h reached the peak, the number of RGMa positive expression increased most obviously, slightly decreased in the following 72h, but compared with the normal control group. The expression of RGMa protein in bilateral cerebellar hemisphere was similar to that of the infarct core region. The mean gray value of RGMa protein expression in the cerebellar cerebellum was higher than that of the ipsilateral cerebellar hemisphere. The positive expression of RGMa protein was found in the choroid plexus, the perivascular, the cerebellar Purkinje cells and the brainstem neurons in the control group.
3, the up regulation of RGMa protein was negatively correlated with the decrease of FA value (P0.05, r=-0.341).
conclusion
1, after supratentorial cerebral infarction, there can be neurotic dysfunction in remote areas.
2, the distant site diffusion parameters change with the core changes of supratentorial infarction, which indirectly indicates that neurologic inability may be related to the nerve conduction pathway.
3, after cerebral ischemia, the expression of RGMa protein was up-regulated, indicating that RGMa participates in axonal regeneration and repair.
4, the changes of RGMa protein and MRI diffusion parameters in bilateral cerebellum proved that cross cerebellar nervous function connection could not exist.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R743.33;R445.2

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本文編號(hào)：1990308