本文選題：小鼠 + 腦缺血再灌注損傷��； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：腦缺血再灌注損傷是一個多種致病因子參與的復(fù)雜病理生理過程，該損傷的分子生物學(xué)機(jī)制至今尚未能夠徹底闡明；缺血性腦血管病嚴(yán)重威脅著人類的健康，現(xiàn)代醫(yī)學(xué)對于缺血性腦卒中的常規(guī)療法療效不佳，毒副作用大，急需開發(fā)低毒高效的藥物。 本文主要研究了小鼠局灶性腦缺血再灌注模型的改良方法以及二氫楊梅素對腦缺血再灌注損傷的保護(hù)作用，并證實(shí)了此種保護(hù)作用與其抗氧化功效相關(guān)。試圖為拓展DMY在臨床上對于缺血性腦卒中的應(yīng)用、開發(fā)低毒高效的抗卒中藥物，奠定良好的模型基礎(chǔ)，并提供實(shí)驗(yàn)數(shù)據(jù)支持。 第一部分小鼠局灶性腦缺血再灌注模型的建立與評價(jià) 目的：建立小鼠局灶性腦缺血再灌注(I/R)模型并予以評價(jià)。 方法：雄性昆明小鼠60只隨機(jī)分為假手術(shù)組30只，I/R模型組30只。改良線栓法制備小鼠大腦中動脈阻塞/再灌注（MCAO/R）模型。通過神經(jīng)行為學(xué)評分、氯化三苯基四氮唑（TTC）染色法測定腦梗死比（%）、干濕重法測定腦含水量（%）及HE染色觀察腦組織病理改變評價(jià)模型可靠性。 結(jié)果：模型存活率為83.33%，總成功率為76.67％。假手術(shù)組小鼠神經(jīng)行為學(xué)評分為（0±0）分，腦梗死比為（0±0）％，腦含水量（77.29±0.45）%。I/R模型組小鼠神經(jīng)行為學(xué)評分為（2.42±0.63）分，腦梗死比為（23.03±3.42）％，腦含水量（83.18±1.65）%，均較假手術(shù)組明顯增高（P0.01）；病理檢查出現(xiàn)典型腦梗死病理改變。 結(jié)論:改良線栓法成功建立簡便、可靠的小鼠局灶性腦缺血再灌注模型。 第二部分二氫楊梅素對小鼠局灶性腦缺血再灌注損傷的保護(hù)作用 目的：研究二氫楊梅素(Dihydromyricetin，DMY)對局灶性腦缺血再灌注(I/R)損傷的保護(hù)作用。 方法：雄性昆明種小鼠隨機(jī)分為4組，，即假手術(shù)組、I/R模型組及DMY高、低劑量組。模型組和DMY組采用線栓法建立左側(cè)大腦中動脈阻塞(middle cerebral artery occlusion, MCAO)3h/再灌注24h局灶性腦缺血再灌注損傷模型；假手術(shù)組僅結(jié)扎左側(cè)頸總動脈，不插入線栓。DMY高、低劑量組分別在造模前10d持續(xù)灌胃DMY500、250mg kg-1，并在缺血前1h、再灌注前1h及再灌注后6h、12h分別灌胃1次；缺血再灌注組和假手術(shù)組則同期灌胃等體積0.5%羧甲基纖維素鈉。再灌注24后，觀察小鼠神經(jīng)功能缺損癥狀評分，取腦行TTC染色測定腦梗死比（%）、干濕重法測定腦含水量（%），HE染色觀察腦組織病理學(xué)變化，計(jì)數(shù)皮層半暗帶區(qū)神經(jīng)元數(shù)目。結(jié)果：與模型組比較，DMY250mg kg-1500mg kg-1組均能降低腦缺血損傷后腦梗死比；DMY500mg kg-1組還可降低神經(jīng)功能缺損評分和腦含水量，改善腦組織病理形態(tài)，增加皮層半暗帶區(qū)神經(jīng)元數(shù)量（P 0.05或P 0.01）。結(jié)論：DMY對小鼠局灶性腦缺血再灌注損傷具有一定的保護(hù)作用。 第三部分二氫楊梅素對小鼠局灶性腦缺血再灌注的抗氧化保護(hù)機(jī)制研究 目的：研究二氫楊梅素（DMY）對局灶性腦缺血再灌注損傷的抗氧化保護(hù)機(jī)制。 方法：雄性昆明種小鼠40只隨機(jī)分為4組，即假手術(shù)組、I/R模型組及DMY高、低劑量組，每組10只。MCAO模型建立和DMY給藥方法同“第二部分”。缺血3h再灌注24h后，分別測定各組小鼠缺血側(cè)腦組織中MDA含量和SOD、GSH-PX的活力。 結(jié)果：與模型組比較，DMY500mg kg-1組能明顯降低腦缺血損傷后腦組織MDA水平（P 0.01），增加I/R損傷后腦組織中t-SOD和GSH-PX的水平（P 0.01）。 結(jié)論：DMY保護(hù)小鼠局灶性腦I/R損傷與其抗氧化作用有關(guān)。
[Abstract]:Cerebral ischemia-reperfusion injury is a complex pathophysiological process involving a variety of pathogenic factors. The molecular biological mechanism of this injury has not yet been fully elucidated. Ischemic cerebrovascular disease is a serious threat to human health. The conventional therapy for ischemic stroke is not effective in modern medicine, toxic and side effects, and need to be developed in urgent need of low development. A drug that is highly toxic and efficient.
This article mainly studied the improved method of focal cerebral ischemia reperfusion model in mice and the protective effect of two hydrogen myricetin on cerebral ischemia reperfusion injury, and confirmed that this protective effect is related to its antioxidation effect. The purpose of this study is to develop the clinical application of DMY for ischemic stroke and develop low toxic and efficient anti stroke drugs. Lay a good foundation for the model and provide experimental data support.
Part one establishment and evaluation of focal cerebral ischemia-reperfusion model in mice
Objective: to establish a mouse model of focal cerebral ischemia-reperfusion (I/R) and evaluate it.
Methods: 60 male Kunming mice were randomly divided into 30 sham operation group and 30 I/R model group. The modified line embolus method was used to prepare the middle cerebral artery occlusion / reperfusion (MCAO/R) model in mice. The cerebral infarction ratio (%) was measured by the neurobehavioral score, three phenyl tetrazolium chloride (TTC) staining method was used to determine the brain water content (%) and the HE staining was used to observe the brain group. The evaluation model of pathological changes was reliable.
Results: the survival rate of the model was 83.33%, the total success rate was (0 + 0), cerebral infarction ratio (0 + 0)%, cerebral water content (77.29 + 0.45) model group (2.42 + 0.63), cerebral infarction ratio (23.03 + 3.42)%, cerebral water content (23.03 + 0)%, and cerebral water content (83.18 + 1.65)%, compared with sham operation group (0 + 0)% (0 + 0)% of the mice in 76.67%. sham operation group. Obviously increased (P0.01); pathological examination showed typical pathological changes of cerebral infarction.
Conclusion: a simple and reliable model of focal cerebral ischemia-reperfusion in mice was successfully established by modified thread embolism.
The second part: protective effect of two hydrogen myricetin on focal cerebral ischemia-reperfusion injury in mice
Objective: To study the protective effect of two Dihydromyricetin (DMY) on focal cerebral ischemia reperfusion (I/R) injury.
Methods: male Kunming mice were randomly divided into 4 groups: the sham operation group, the I/R model group and the DMY high, low dose group. The model group and the DMY group were used to establish the left middle cerebral artery occlusion (middle cerebral artery occlusion, MCAO) 3h/ reperfusion 24h focal cerebral ischemia reperfusion injury model, and the sham operation group only ligated the left cervical total movement. The.DMY was high in the vein, without the insertion of the thread embolus, and the low dose group continued to intrigastrate DMY500250mg kg-1 before the model, and before the ischemia, 1H, 1H and reperfusion before reperfusion, 6h, 12h respectively 1 times; the ischemia reperfusion group and the sham operation group had the same volume of 0.5% carboxymethyl cellulose in the same volume. After reperfusion 24, the evaluation of the symptoms of neural function defect in mice was evaluated. TTC staining was used to determine cerebral infarction ratio (%), dry wet weight method was used to determine brain water content (%), HE staining was used to observe the pathological changes of brain tissue and count the number of neurons in the cortical semi dark zone. Results: compared with the model group, the DMY250mg kg-1500mg kg-1 group could reduce the death ratio of cerebral infarction after cerebral ischemia injury, and the DMY500mg kg-1 group could also reduce the neurological function deficiency. Loss of score and brain water content, improve the pathological morphology of brain tissue and increase the number of neurons in the cortical semi dark zone (P 0.05 or P 0.01). Conclusion: DMY has a certain protective effect on focal cerebral ischemia reperfusion injury in mice.
The third part of the protective mechanism of two hydrogen myricetin on focal cerebral ischemia-reperfusion in mice
Objective: To study the antioxidant mechanism of two hydrogen myricetin (DMY) on focal cerebral ischemia-reperfusion injury.
Methods: 40 male Kunming mice were randomly divided into 4 groups: the sham operation group, the I/R model group and the DMY high, low dose group, 10.MCAO models in each group and the second part of the DMY administration method. After the ischemia 3H reperfusion 24h, the MDA content and SOD and GSH-PX activity in the ischemic side of the mice were measured respectively.
Results: compared with the model group, DMY500mg kg-1 group could significantly reduce the level of MDA (P 0.01) after cerebral ischemia injury and increase the level of t-SOD and GSH-PX in the brain tissue after I/R injury (P 0.01).
Conclusion: DMY protects mice from focal brain I/R damage and its antioxidant effect.

【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R743.31

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本文編號：1812004