本文選題：腦缺血再灌注損傷　切入點(diǎn)：大腦中動脈閉塞　出處：《蘇州大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

【摘要】：背景與目的 缺血性腦血管病(Ischemic Cerebral Vesscular Disease,ICVD)是神經(jīng)科常見病多發(fā)病,在ICVD的治療中重建血流或增強(qiáng)缺血區(qū)的血流供應(yīng)是缺血腦組織修復(fù)損傷的必需條件,但同時帶來的再灌注損傷也是目前最受關(guān)注的問題。線栓法大鼠大腦中動脈閉塞(middle cerebral artery occlusion, MCAO)模型能最大程度模擬人類缺血性卒中發(fā)生,被廣泛用于實驗性腦缺血再灌注(Ischemia-reperfusion ,IR)損傷的研究。國內(nèi)外大量實驗證實,MK-801(dizocilpine)在實驗性腦缺血模型中具有重要的神經(jīng)保護(hù)作用。 本實驗用周齡和性別匹配的SD大鼠成功建立了MCAO動物模型,對原有線栓法大腦中動脈閉塞模型進(jìn)行了改進(jìn),并用MK-801預(yù)處理進(jìn)一步驗證動物模型,為研究腦缺血再灌注損傷的發(fā)病機(jī)理和研制治療藥物打下基礎(chǔ)。 方法 50只雄性SD大鼠隨機(jī)分為3組,IR組、p-MCAO(permanent MCAO)組及假手術(shù)組(10只)。IR組(n=22)分為2個亞組,IR治療組(12只)及IR模型組(10只)。p-MCAO組(n=18)也分為2個亞組,p-MCAO治療組(10只)及p-MCAO模型組(8只)。兩治療組將藥物MK-801(0.5mg/Kg,溶于二甲基亞砜:0.9%生理鹽水,體積比為1:39的混合溶液中)于腦缺血15分鐘前經(jīng)頸外動脈給藥。假手術(shù)組、兩模型組大鼠僅給予等容量溶劑。手術(shù)組以線栓法制備MCAO模型,假手術(shù)組接受相同手術(shù)流程,但不插入線栓。手術(shù)后分別對各組大鼠做神經(jīng)功能缺損評分,隨后取各大鼠大腦冠狀位切片行TTC染色以測量腦梗死及水腫體積,冰凍切片焦油紫染色觀察大鼠大腦皮層區(qū)細(xì)胞損傷程度,酶聯(lián)免疫吸附法測定腦中腫瘤壞死因子α(TNF-α)含量。 結(jié)果 1.各手術(shù)組大鼠出現(xiàn)嚴(yán)重的神經(jīng)功能障礙,假手術(shù)組大鼠則無任何臨床癥狀。且神經(jīng)行為學(xué)評分顯示IR治療組大鼠神經(jīng)功能明顯優(yōu)于IR模型組。 2.切片TTC、焦油紫染色各手術(shù)組大鼠腦組織見明顯腦梗死灶,假手術(shù)組大鼠無此改變。IR治療組腦梗塞體積較IR模型組明顯減小。 3.對大鼠腦組織生化指標(biāo)檢測發(fā)現(xiàn),手術(shù)組大鼠的TNF-α的表達(dá)明顯增加。與IR模型組相比,IR治療組大鼠TNF-α的含量有所降低(P0.01)。 結(jié)論 1.本實驗建立的大鼠模型在臨床表現(xiàn)、病理變化等方面符合MCAO模型的表現(xiàn),模型穩(wěn)定、可靠,是研究腦缺血再灌注損傷的理想動物模型。 2. MK-801能改善腦缺血再灌注損傷大鼠的神經(jīng)功能障礙,減輕缺血區(qū)的腦梗死,并減少炎癥因子TNF-α的產(chǎn)生,具有明顯的改善腦缺血再灌注損傷的作用。
[Abstract]:Background and purpose. Ischemic Cerebral Vesscular disease (ICVD) is a common disease in neurology. In the treatment of ICVD, it is necessary to reconstruct the blood flow or increase the blood flow supply in the ischemic area. The middle cerebral artery occlusion (MCAO) model of middle cerebral artery occlusion (MCAO) can best mimic the occurrence of ischemic stroke in humans. MK-801 dizocilpine has been widely used in the study of experimental cerebral ischemia-reperfusion injury. A large number of experiments at home and abroad have confirmed that MK-801 dizocilpine plays an important role in the neuroprotection of experimental cerebral ischemia model. In this experiment, MCAO animal model was successfully established by week old and sex matched SD rats, the original middle cerebral artery occlusion model was improved, and the animal model was further verified by MK-801 pretreatment. To study the pathogenesis of cerebral ischemia-reperfusion injury and the development of treatment drugs. Method. 50 male Sprague-Dawley rats were randomly divided into 3 groups: ir group (n = 10) and sham-operated group (n = 10). They were divided into 2 subgroups (n = 12) and IR group (n = 10) and IR model group (n = 10). They were also divided into 2 subgroups (n = 10) and p-MCAO treatment group (n = 10) and p-MCAO model group (n = 10) and p-MCAO model group (n = 10). In the two treatment groups, the drug MK-801 + 0.5 mg / kg was dissolved in 0.9% normal saline of dimethyl sulfoxide (DMSO). The rats in sham-operated group and two model groups were given the same volume solvent only. The MCAO model was made by thread embolization in the operation group, and the sham-operation group received the same operation procedure. However, no thread embolus was inserted. After the operation, the neurological impairment scores were scored in each group of rats respectively. The coronal sections of the brain of each group were then taken for TTC staining to measure the volume of cerebral infarction and edema. The degree of cell injury in rat cerebral cortex was observed by tar violet staining and the content of TNF- 偽 in brain was determined by enzyme linked immunosorbent assay (Elisa). Results. 1. There were severe neurological dysfunction in each operation group, but no clinical symptoms in sham-operation group, and neurobehavioral score showed that the nerve function of IR group was better than that of IR model group. 2. There were obvious cerebral infarction in brain tissue of rats in each operation group stained with TTCand tar violet, but no change was found in sham-operated group. The infarct volume in IR treatment group was significantly smaller than that in IR model group. 3. It was found that the expression of TNF- 偽 in the operation group was significantly higher than that in the IR model group, and the content of TNF- 偽 in the IR treatment group was lower than that in the IR model group. Conclusion. 1. The rat model established in this study accords with the MCAO model in clinical manifestations and pathological changes. The model is stable and reliable. It is an ideal animal model for the study of cerebral ischemia-reperfusion injury. 2. MK-801 can improve the neurological dysfunction of rats with cerebral ischemia reperfusion injury, reduce the cerebral infarction in the ischemic area, and reduce the production of inflammatory factor TNF- 偽, which can obviously improve the cerebral ischemia-reperfusion injury.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R743;R-332

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 侯紹章;甘草酸二銨對小鼠腦缺血再灌注損傷的保護(hù)作用及機(jī)制研究[D];南京中醫(yī)藥大學(xué);2012年

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本文編號：1588190