發(fā)布時(shí)間：2018-05-28 03:09

  本文選題：亞低溫(mildhypothemia) + 缺氧缺血性腦損傷(HIBD)　； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：新生兒缺氧缺血性腦�。╤ypoxic-ischemic encephalopathy,HIE）是由于圍產(chǎn)期窒息缺氧所引起的神經(jīng)系統(tǒng)損傷，是新生兒時(shí)期最常見的疾病之一，為嬰幼兒永久性神經(jīng)系統(tǒng)功能障礙甚至是導(dǎo)致新生兒死亡的重要原因�，F(xiàn)階段臨床上的藥物療法療效甚微。本文的目的是在成功建立新生大鼠缺氧缺血性腦損傷（hypoxic-ischemic brain damage,HIBD）動(dòng)物模型后，立刻給予全身性亞低溫（mild hypothemia）治療，在不同的時(shí)間點(diǎn)檢測不同組別新生大鼠患側(cè)腦組織Bax及HIF-1α基因的表達(dá)并探究兩者之間的關(guān)系。試圖闡明亞低溫干預(yù)在治療新生大鼠HIBD時(shí)可能的神經(jīng)保護(hù)機(jī)制，為現(xiàn)階段臨床上治療新生兒HIE提供更進(jìn)一步的理論依據(jù)。 方法：新生7日齡SD大鼠120只，雌雄不拘，隨機(jī)分成三組：假手術(shù)組（A組），常溫組（B組），亞低溫組（C組），每組各40只。B組和C組均需先制備HIBD動(dòng)物模型。三組均根據(jù)實(shí)驗(yàn)要求即處死時(shí)間點(diǎn)的不同分為2h組、6h組、12h組、24h組、48h組5個(gè)亞組，每亞組各8只。B組和C組新生大鼠均采用阻斷左側(cè)頸總動(dòng)脈，后放置于含8%O2+92%NO2的環(huán)境中缺氧2h制備動(dòng)物模型，其過程中進(jìn)行行為學(xué)觀察；C組新生大鼠HIBD模型制備成功后立刻予全身性亞低溫處理。各組根據(jù)實(shí)驗(yàn)要求采用斷頭法提取腦組織。觀察腦組織大體形態(tài)變化，采用實(shí)時(shí)熒光定量PCR（real-timePCRRT-PCR）法分別檢測不同組別新生大鼠各時(shí)間點(diǎn)患側(cè)腦組織Bax及HIF-1α基因表達(dá)變化，記錄統(tǒng)計(jì)結(jié)果，行統(tǒng)計(jì)學(xué)分析。 結(jié)果：（1）行HIBD造模的新生大鼠前后均出現(xiàn)了異常的行為活動(dòng)。（2）肉眼觀察B組患側(cè)腦組織各時(shí)間點(diǎn)均出現(xiàn)明顯水腫，，而C組腦組織各時(shí)間點(diǎn)無水腫。（3）BaxmRNA的表達(dá)：A組新生大鼠腦組織各時(shí)間點(diǎn)BaxmRNA的表達(dá)甚微。B組新生大鼠腦組織各時(shí)間點(diǎn)BaxmRNA表達(dá)2h上調(diào)且逐漸增加，12h達(dá)高峰，12h-48h維持在高峰。C組新生大鼠腦組織各時(shí)間點(diǎn)BaxmRNA的表達(dá)2h出現(xiàn)下降趨勢并于6h達(dá)到最低水平，后期稍升高，即12h~48h，BaxmRNA的表達(dá)出現(xiàn)微升高。（4）HIF-1αmRNA表達(dá)：A組新生大鼠腦組織各時(shí)間點(diǎn)HIF-1αmRNA的表達(dá)偏少，B組新生大鼠腦組織各時(shí)間點(diǎn)HIF-1αmRNA表達(dá)2h出現(xiàn)升高且逐漸增加，48h達(dá)到高峰；C組新生大鼠腦組織各時(shí)間點(diǎn)HIF-1αmRNA表達(dá)2h稍升高，后期呈逐漸降低趨勢。 結(jié)論：（1）新生大鼠HIBD后予亞低溫干預(yù)，可使HIBD后腦組織的水腫程度減輕，以提示亞低溫干預(yù)對(duì)新生大鼠HIBD后的神經(jīng)系統(tǒng)可能發(fā)揮保護(hù)性作用。（2）亞低溫可能抑制促凋亡基因BaxmRNA表達(dá)，減輕HIBD后的病理損傷過程，從而抑制神經(jīng)細(xì)胞凋亡。（3）亞低溫干預(yù)后期HIF-1αmRNA的表達(dá)使下游促凋亡基因BaxmRNA表達(dá)較前略有增加，從而清除HIBD后腦組織已凋亡細(xì)胞，對(duì)新生大鼠HIBD后的神經(jīng)系統(tǒng)起到一定的保護(hù)作用，從而為新生兒HIE提供新的臨床診療思路。
[Abstract]:Objective: Hypoxic-ischemic encephalopathy (HIEE) is a nervous system injury caused by perinatal asphyxia and is one of the most common diseases in neonatal period. Permanent neurological dysfunction is an important cause of neonatal death. At this stage, the clinical efficacy of drug therapy is minimal. The aim of this study was to treat neonatal rats with hypoxic-ischemic brain damage (HIBD) with mild hypothermia immediately after the establishment of HIBD model. The expression of Bax and HIF-1 偽 genes in brain tissue of different groups of newborn rats were detected at different time points and the relationship between them was explored. This paper attempts to elucidate the possible neuroprotective mechanism of mild hypothermia intervention in the treatment of neonatal HIBD in order to provide a further theoretical basis for the clinical treatment of neonatal HIE at this stage. Methods: 120 male and female Sprague-Dawley rats of 7 days old were randomly divided into three groups: sham operation group (group A), normal temperature group (group B) and mild hypothermia group (group C). According to the requirements of the experiment, the three groups were divided into 5 subgroups, including 2 h group, 6 h group, 12 h group, 24 h group, 48 h group, 8 rats in each subgroup, 8 rats in group B and group C, all of which were treated with occlusion of left common carotid artery. The animal model was established by hypoxia for 2 hours in the environment containing 8%O2 92%NO2. During the course of behavioral observation, the HIBD model of neonatal rats in group C was treated with systemic mild hypothermia immediately after the establishment of HIBD model. According to the requirements of the experiment, the brain tissue was extracted by head-cut method in each group. The changes of Bax and HIF-1 偽 gene expression in brain tissue of different groups of neonatal rats were detected by real-time PCR RT-PCRmethod. The statistical results were recorded and analyzed statistically. Results (1) abnormal behavioral activity was observed before and after HIBD modeling in newborn rats. (1) the brain tissue of the affected side of group B showed obvious edema at every time point after observation with naked eyes. The expression of BaxmRNA in brain tissue of neonatal rats in group C was minimal at each time point. The expression of BaxmRNA in brain tissue of group B was up-regulated for 2 h and gradually increased at 12 h to reach the peak at 12 h and maintained at the peak at 48 h. In group C, the expression of BaxmRNA in brain tissue of neonatal rats decreased at 2 h and reached the lowest level at 6 h. Later, a little higher, The expression of HIF-1 偽 mRNA in brain tissue of neonatal rats in group A was slightly increased at 12 h and 48 h. The expression of HIF-1 偽 mRNA in brain tissue of neonatal rats in group A was slightly lower than that in group B and the expression of HIF-1 偽 mRNA in brain tissue of neonatal rats in group B increased for 2 h and gradually increased to the peak at 48 h. The expression of HIF-1 偽 mRNA in the brain of neonatal rats in group C reached the peak at 48 h. The expression of HIF-1 偽 mRNA increased slightly at different time points. In the later stage, the trend was decreasing gradually. Conclusion (1) mild hypothermia intervention after HIBD in neonatal rats can reduce the edema of brain tissue after HIBD, which suggests that mild hypothermia intervention may play a protective role in the nervous system after HIBD in neonatal rats. 2) mild hypothermia may inhibit the expression of pro-apoptotic gene BaxmRNA. After mild hypothermia intervention, the expression of HIF-1 偽 mRNA increased slightly, and the BaxmRNA expression of the downstream apoptotic gene increased slightly, thus eliminating the apoptotic cells in brain tissue after HIBD. It can protect the nervous system of newborn rats after HIBD and provide a new way of clinical diagnosis and treatment for neonatal HIE.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742

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