本文選題：瑞香素 + 腦缺血再灌注��； 參考：《蘇州大學》2014年碩士論文

【摘要】：第一部分瑞香素（Daphnetin）對小鼠大腦中動脈缺血再灌注損傷及新生大鼠缺氧缺血性損傷的保護作用 目的：觀察瑞香素(Daphnetin, DAP)對小鼠大腦中動脈缺血再灌注損傷及新生大鼠缺氧缺血性損傷是否具有保護作用。 方法：將雄性ICR小鼠及新生SD大鼠隨機分為安慰劑(sham)組、安慰劑+DAP組、安慰劑+缺血再灌注(ischemia/reperfusion, I/R)(or缺氧缺血(hypoxia/ischemia, H/I))組和DAP+I/R(or H/I)組，建立小鼠短暫大腦中動脈阻塞(transient middle cerebral arteryocclusion, tMCAO)模型及新生大鼠缺氧缺血(H/I)模型，觀察DAP的處理對小鼠腦梗死體積、神經(jīng)行為功能及對新生大鼠缺氧缺血性腦梗死的影響。 結果：與對照組相比，經(jīng)DAP處理后小鼠的腦梗死體積明顯減小，神經(jīng)行為功能明顯增強(P0.05)。缺血再灌注前側腦室預給予DAP(1mg/kg)，腦梗死體積減小了24.6%；神經(jīng)行為學評分具有明顯統(tǒng)計學差異(P0.05)。同樣，缺血再灌注后不同時間段分別予以腹腔注入DAP(10mg/kg)，與對照組相比，經(jīng)DAP預處理后的新生大鼠的腦梗死體積明顯縮小，甚至缺血4小時后給藥仍有保護作用(P0.05)。 結論：使用DAP干預小鼠tMCAO模型及新生大鼠H/I模型，小鼠的腦梗死體積明顯減小，，神經(jīng)行為功能缺損明顯減輕；新生大鼠的腦梗死體積明顯減少。這些結果均提示DAP對于小鼠tMCAO及新生大鼠H/I誘導的腦缺血損傷具有神經(jīng)保護作用。 第二部分瑞香素（Daphnetin）對HT22細胞中谷氨酸毒性損傷的保護作用的相關機制 目的：研究瑞香素(Daphnetin, DAP)對HT22細胞中谷氨酸毒性的保護及對谷胱甘肽(Glutathione, GSH)及超氧化物歧化酶(superoxide dismutase, SOD)的影響。探討DAP神經(jīng)保護作用的相關機制。 方法：將HT22細胞培養(yǎng)過夜，后加入5mmol/L谷氨酸制作神經(jīng)元損傷模型組。培養(yǎng)基中加入不同濃度的DAP與培養(yǎng)基的混合液共同孵育12小時，后在顯微鏡下分別觀察各組神經(jīng)元形態(tài)變化；采用MTS法檢測細胞活力；測定細胞內GSH含量及SOD活力的變化。 結果： DAP能有效地提高HT22細胞的存活率，其最佳保護濃度是100μmol/L。以5mmol/L谷氨酸作用于培養(yǎng)HT22細胞，細胞形態(tài)表現(xiàn)為突起減少。應用DAP100μmol/L后可改善因谷氨酸引起的HT22細胞形態(tài)的改變，可維持谷氨酸損傷后HT22細胞內GSH的含量及SOD的活性。 結論： DAP可明顯拮抗谷氨酸毒性作用。其可能的機制與DAP維持GSH含量及SOD活性有關。
[Abstract]:The Protective effect of Daphnetin on Middle Cerebral artery Ischemia-reperfusion injury in mice and Hypoxic-Ischemic injury in Neonatal Rats Aim: to observe the protective effect of daphnetin (DAP1) on middle cerebral artery ischemia reperfusion injury in mice and hypoxic ischemic injury in newborn rats. Methods: male ICR mice and newborn SD rats were randomly divided into three groups: the placebo group, the placebo DAP group, the placebo DAP group, the placebo ischemia reperfusion group, the I/R)(or hypoxic ischemia hypoxia-r-ischemic ischemic reperfusion group, and the DAP I/R(or ischemia reperfusion group. The transient middle cerebral arterial occlusion (tMCAO) model of transient middle cerebral artery occlusion (TMCAO) in mice and the model of hypoxic-ischemic H / I in neonatal rats were established to observe the effects of DAP treatment on cerebral infarction volume, neurobehavioral function and hypoxic-ischemic cerebral infarction in neonatal rats. Results: compared with the control group, the volume of cerebral infarction and the neurobehavioral function of the mice treated with DAP were significantly decreased and the neurobehavioral function was significantly enhanced (P 0.05). The volume of cerebral infarction decreased by 24.6mg 路kg ~ (-1) 路kg ~ (-1) and the neurobehavioral score was significantly different (P _ (0.05) ~ 0. 05) when the anterior ventricle was given 1 mg 路kg ~ (-1) of DAPG / kg after ischemia-reperfusion. Similarly, 10 mg / kg DAP was injected intraperitoneally at different time points after ischemia / reperfusion. Compared with the control group, the volume of cerebral infarction in neonatal rats pretreated with DAP was significantly reduced, and even after 4 hours of ischemia, the drug still had a protective effect (P 0.05). Conclusion: the cerebral infarct volume and neurobehavioral deficit were significantly decreased and the cerebral infarction volume of newborn rats was significantly decreased after DAP was used to interfere with tMCAO model and neonatal rat model of H / P I. These results suggest that DAP has neuroprotective effects on cerebral ischemia injury induced by tMCAO in mice and H / P I in newborn rats. Part two the protective mechanism of daphnetin on glutamate toxicity in HT22 cells Aim: to study the protection of daphnetin (DAPs) against glutamate toxicity in HT22 cells and its effects on glutathione (GSH) and superoxide dismutase (sod). To explore the mechanism of neuroprotective effect of DAP. Methods: HT22 cells were cultured overnight and 5mmol/L glutamate was added to model group. Different concentrations of DAP were added to the culture medium for 12 hours, then the morphological changes of neurons were observed under microscope, the cell viability was detected by MTS assay, and the changes of GSH content and SOD activity in the cells were measured. Results: DAP could effectively improve the survival rate of HT22 cells, and the best protective concentration was 100 渭 mol / L. When 5mmol/L glutamate was used to culture HT22 cells, the morphology of the cells decreased. DAP100 渭 mol/L could improve the morphological changes of HT22 cells induced by glutamate, and maintain the content of GSH and the activity of SOD in HT22 cells after Glutamic acid injury. Conclusion: DAP can antagonize the toxicity of glutamate. The possible mechanism is related to the maintenance of GSH content and SOD activity by DAP.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R743.31

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