本文選題：ABT-702 + 缺血再灌注��； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景缺血性腦血管病的發(fā)病率近年來呈逐年遞升的趨勢(shì),給人類身體健康和生存質(zhì)量帶來極大的危害,因而對(duì)該病不斷深入和細(xì)致地研究,成為神經(jīng)學(xué)科科學(xué)家研究的熱門方向,不斷尋求新的治療靶點(diǎn),盡早挽救缺血半暗帶成為目前缺血性腦血管病研究的重點(diǎn)之一。研究發(fā)現(xiàn)腺苷對(duì)缺血性腦血管病具有保護(hù)作用,ABT-702作為新型的非核苷類腺苷激酶抑制劑(Adenosine Kinase Inhibitors AKI),能夠提高體內(nèi)腺苷(Adenosion Ado)水平,在既往的研究中,研究者們證實(shí)了ABT-702在許多人類疾病中具有治療或保護(hù)作用,但是ABT-702在缺血性腦血管病中的作用卻暫無文獻(xiàn)報(bào)道。目的探討在大鼠腦缺血性再灌注損傷模型中,腺苷激酶抑制劑ABT-702應(yīng)用后,大鼠大腦腦組織中腺苷含量的變化,以及自噬蛋白Beclin1的表達(dá)情況,進(jìn)一步驗(yàn)證ABT-702對(duì)大腦具有保護(hù)作用,為其在缺血性腦血管病中的研究及應(yīng)用提供前沿基礎(chǔ)。方法雄性SD大鼠84只,隨機(jī)分為對(duì)照組、假手術(shù)組、模型組、ABT-702組四個(gè)組,每組21只,所有大鼠在再灌注后均進(jìn)行大鼠神經(jīng)功能缺失評(píng)分,每組選取6只進(jìn)行TTC染色檢測(cè)梗死面積,各組再隨機(jī)選取9只分為3個(gè)亞組,在不同時(shí)間點(diǎn)通過高效液相色譜法(High Performance Liquid Chromatography HPLC)檢測(cè)腦組織腺苷含量,最后各組再隨機(jī)選取6只通過RT-PCR法檢測(cè)Beclin1的表達(dá)。結(jié)果1、ABT-702組神經(jīng)缺失功能評(píng)分低于模型組。通過Zea Longa法進(jìn)行評(píng)分后,對(duì)照組和假手術(shù)組評(píng)分均為0分,模型組與ABT-702組均有神經(jīng)功能缺失癥狀,但ABT-702神經(jīng)功能缺失評(píng)分低于模型組,差距具有統(tǒng)計(jì)學(xué)意義(P0.05)。2、ABT-702組的梗死體積明顯低于模型組。對(duì)照組及假手術(shù)組TTC染色后未見梗死區(qū)域,模型組及ABT-702組均可見大片梗死區(qū)域(TTC染色后為白色)。但ABT-702組梗死體積與模型組相比,梗死體積小于模型組,差距具有統(tǒng)計(jì)學(xué)意義(P0.05)。3、HPLC法檢測(cè)大鼠大腦腺苷含量變化。各組在再灌注后,分別通過HPLC法在不同時(shí)間點(diǎn)(2h、6h、12h)進(jìn)行腦組織中腺苷含量檢測(cè)。結(jié)果提示,各組在各時(shí)間點(diǎn)均可以檢測(cè)處腺苷的存在。對(duì)照組與假手術(shù)組兩組對(duì)比,在各時(shí)間點(diǎn)腺苷含量水平?jīng)]有差距,模型組與ABT-702組在再灌注2h、6h時(shí)腺苷含量均高于對(duì)照組與假手術(shù)組組。ABT-702組與模型組對(duì)比,ABT-702組在再灌注各時(shí)間段腺苷含量水平均高于模型組。但是在再灌注12h后時(shí)ABT-702組的腺苷含量水平低于本組再灌注后2h及6h時(shí)的水平。4、腦組織中Beclin1 mRNA表達(dá)。各組在再灌注6h后,Beclin1 mRNA均有表達(dá),但模型組Beclin1蛋白的表達(dá)量高于對(duì)照組與假手術(shù)組。而ABT-702組的Beclin1表達(dá)量明顯高于其它三組。結(jié)論1、ABT-702在大鼠缺血再灌注損傷中具有保護(hù)作用,減輕了大鼠神經(jīng)功能的損傷,減小了大鼠腦組織的梗死體積;2、ABT-702應(yīng)用后大鼠腦組織內(nèi)腺苷含量明顯增加,并且在再灌注6h時(shí)腦組織腺苷含量最高;3、ABT-702在大鼠缺血再灌注模型中,提高了自噬(Autophagy)相關(guān)蛋白Beclin1的表達(dá)水平,這可能是ABT-702在大鼠缺血再灌注損傷(Cerebral Ischemia Reperfusion Injury,CIRI)中起保護(hù)作用的機(jī)制之一。
[Abstract]:The incidence of background ischemic cerebrovascular disease has been increasing year by year, which has brought great harm to the health and quality of life of human being. Therefore, it has become a hot direction in the research of neuroscientists, seeking new therapeutic targets and saving the ischemic penumbra as soon as possible. One of the key points in the study of bloody cerebrovascular disease. The study found that adenosine has a protective effect on ischemic cerebrovascular disease. ABT-702, as a new non nucleoside adenosine kinase inhibitor (Adenosine Kinase Inhibitors AKI), can improve the level of adenosine (Adenosion Ado) in the body. In the previous study, researchers confirmed that ABT-702 is in many people. However, the role of ABT-702 in ischemic cerebrovascular disease is not reported. Objective to explore the changes of adenosine content in the brain tissue of rat brain and the expression of autophagin Beclin1 in rat brain tissue after the application of adenosine kinase inhibitor ABT-702 in the rat model of ischemic cerebral reperfusion injury. One step was to verify the protective effect of ABT-702 on the brain and provide the Frontier Foundation for its research and application in ischemic cerebrovascular disease. Methods 84 male SD rats were randomly divided into control group, sham operation group, model group and group ABT-702, with four groups of 21 rats in each group. All rats were scored in each group after reinjection, each group was selected. The infarct area was detected by TTC staining in 6 rats, and 9 groups were randomly selected to be divided into 3 subgroups, and the content of adenosine in brain tissue was detected by High Performance Liquid Chromatography HPLC at different time points. Finally, 6 rats were randomly selected to detect the expression of Beclin1 by RT-PCR method. Results 1, ABT-702 group nerve deletion. The score of the function score was lower than that of the model group. The scores of the control group and the sham operation group were all 0 points after the Zea Longa method. The model group and the ABT-702 group had the symptoms of neural function deletion, but the score of the ABT-702 neural function loss was lower than the model group, the gap was statistically significant (P0.05).2, and the infarct volume in the group ABT-702 was significantly lower than that of the model group. The infarct area was not found in the sham operation group after TTC staining. The infarct area in the model group and the ABT-702 group were all visible (white after TTC). But the infarct volume in the ABT-702 group was less than the model group, and the infarct volume was statistically significant (P0.05).3. The HPLC method was used to detect the changes in the cerebral adenosine content in the rats. Each group was divided after reperfusion. Do not use HPLC method to detect adenosine content in brain tissue at different time points (2h, 6h, 12h). The results suggest that each group can detect the presence of adenosine at all time points. Compared with the two groups of sham operation group, the level of adenosine content is no difference at all time points, and the adenosine content in the model group and the ABT-702 group is higher than that of the 2H and 6h. In group.ABT-702 and sham group, the level of adenosine content in group ABT-702 was higher than that of model group at all time of reperfusion, but the level of adenosine content in group ABT-702 was lower than that of 2H and 6h after reperfusion after reperfusion of 12h, and the expression of Beclin1 mRNA in brain tissue. After reperfusion for 6h, Beclin1 mRNA was all after reperfusion. The expression of Beclin1 protein in the model group was higher than that of the control group and the sham operation group. The expression of Beclin1 in the ABT-702 group was significantly higher than that of the other three groups. Conclusion 1, ABT-702 has protective effect in the rat ischemia reperfusion injury, alleviates the injury of the nerve function and reduces the infarct volume of the rat brain tissue; 2, ABT-702 after application. The content of adenosine in the rat brain was significantly increased and the content of adenosine in the brain was highest at 6h reperfusion. 3, ABT-702 increased the expression of autophagy (Autophagy) related protein Beclin1 in the rat model of ischemia-reperfusion, which may be the protection of ABT-702 in the ischemia-reperfusion injury (Cerebral Ischemia Reperfusion Injury, CIRI) in rats. One of the mechanisms of protection.

【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.3

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